Journal articles: 'Targeted integration'

1

Amoils, Shannon. "Targeted integration." Nature Reviews Microbiology 4, no. 2 (February 2006): 87. http://dx.doi.org/10.1038/nrmicro1357.

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Tabernero, J., and F. J. Ramos. "305 Integration of targeted therapies." European Journal of Cancer Supplements 7, no. 2 (September 2009): 74. http://dx.doi.org/10.1016/s1359-6349(09)70258-7.

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Shi, Zhaoying, Dandan Tian, Huhu Xin, Jingru Lian, Xiaogang Guo, and Yonglong Chen. "Targeted integration of genes inXenopus tropicalis." genesis 55, no. 1-2 (January 2017): e23006. http://dx.doi.org/10.1002/dvg.23006.

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Bhatt, Shivam, and Ronald Chalmers. "Targeted DNA transposition in vitro using a dCas9-transposase fusion protein." Nucleic Acids Research 47, no. 15 (June 25, 2019): 8126–35. http://dx.doi.org/10.1093/nar/gkz552.

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Abstract Homology-directed genome engineering is limited by transgene size. Although DNA transposons are more efficient with large transgenes, random integrations are potentially mutagenic. Here we present an in vitro mechanistic study that demonstrates efficient Cas9 targeting of the mariner transposon Hsmar1. Integrations were unidirectional and tightly constrained to one side of the sgRNA binding site. Further analysis of the nucleoprotein intermediates demonstrated that the transposase and Cas9 moieties can bind their respective substrates independently or in concert. Kinetic analysis of the reaction in the presence of the Cas9 target–DNA revealed a delay between first and second strand cleavage at the transposon end. This step involves a significant conformational change that may be hindered by the properties of the interdomainal linker. Otherwise, the transposase moiety behaved normally and was proficient for integration in vitro and in Escherichia coli. Specific integration into the lacZ gene in E. coli was obscured by a high background of random integrations. Nevertheless, Cas9 is an attractive candidate for transposon-targeting because it has a high affinity and long dwell-time at its target site. This will facilitate a future optogenetic strategy for the temporal control of integration, which will increase the ratio of targeted to untargeted events.

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Hughes, A. J., R. K. C. Lin, D. M. Peehl, and A. E. Herr. "Microfluidic integration for automated targeted proteomic assays." Proceedings of the National Academy of Sciences 109, no. 16 (April 2, 2012): 5972–77. http://dx.doi.org/10.1073/pnas.1108617109.

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Stephens, Zachary, Daniel O’Brien, Mrunal Dehankar, Lewis R. Roberts, Ravishankar K. Iyer, and Jean-Pierre Kocher. "Exogene: A performant workflow for detecting viral integrations from paired-end next-generation sequencing data." PLOS ONE 16, no. 9 (September 22, 2021): e0250915. http://dx.doi.org/10.1371/journal.pone.0250915.

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The integration of viruses into the human genome is known to be associated with tumorigenesis in many cancers, but the accurate detection of integration breakpoints from short read sequencing data is made difficult by human-viral homologies, viral genome heterogeneity, coverage limitations, and other factors. To address this, we present Exogene, a sensitive and efficient workflow for detecting viral integrations from paired-end next generation sequencing data. Exogene’s read filtering and breakpoint detection strategies yield integration coordinates that are highly concordant with long read validation. We demonstrate this concordance across 6 TCGA Hepatocellular carcinoma (HCC) tumor samples, identifying integrations of hepatitis B virus that are also supported by long reads. Additionally, we applied Exogene to targeted capture data from 426 previously studied HCC samples, achieving 98.9% concordance with existing methods and identifying 238 high-confidence integrations that were not previously reported. Exogene is applicable to multiple types of paired-end sequence data, including genome, exome, RNA-Seq and targeted capture.

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Blumenschein, George R., and Roy S. Herbst. "Integration of Targeted Therapies in Gemcitabine Chemotherapy Regimens." Clinical Lung Cancer 4, no. 4 (January 2003): 217–23. http://dx.doi.org/10.3816/clc.2003.n.001.

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Volis, Sergei. "Species-targeted plant conservation: time for conceptual integration." Israel Journal of Plant Sciences 63, no. 4 (February 6, 2015): 232–49. http://dx.doi.org/10.1080/07929978.2015.1085203.

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To date, there have been only limited attempts to conceptually unify ex situ and in situ approaches as parts of an integrated conservation methodology. This paper is an attempt of such conceptual integration of existing approaches for the efficient conservation of rare and endangered plant species. My integration of available plant conservation biology literature is based on the idea that ecologically significant species genetic variation is of primary importance for plant conservation. This idea is used for providing guidelines about inventory of existing populations, sampling and propagating sampled material, and use of this material in species recovery actions.

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Sun, Duxin. "Nanotheranostics: Integration of Imaging and Targeted Drug Delivery." Molecular Pharmaceutics 7, no. 6 (December 6, 2010): 1879. http://dx.doi.org/10.1021/mp1003652.

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Montini, Eugenio, Daniela Cesana, Manfred Schmidt, Francesca Sanvito, Maurilio Ponzoni, Lucia Sergi Sergi, Fabrizio Benedicenti, et al. "Modeling the Genotoxicity of Viral Vector Integration in a Tumor Prone Hematopoietic Stem Cell Transplantation Model." Blood 108, no. 11 (November 16, 2006): 451. http://dx.doi.org/10.1182/blood.v108.11.451.451.

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Abstract Insertional mutagenesis represents a major hurdle to successful gene therapy and mandates for sensitive pre-clinical assays of genotoxicity. Cdkn2a−/ − mice are defective for p53 and Rb pathways, and are susceptible to a broad range of cancer-triggering genetic lesions. We developed an in-vivo genotoxicity assay, based on transplantation of Cdkn2a−/ − hematopoietic stem cells (HSCs), treated or not with prototypical retroviral (RV) and lentiviral (LV) vectors. In our rationale if RV or LV treatment is genotoxic, transplanted mice will show a significantly earlier tumor onset. Using this approach, we detected a dose-dependent acceleration in tumor onset in the mice transplanted with RV treated cells. We compared the RV and LV integration site distribution in pre-transplant cells and tumors from the transplanted mice. As expected, RV integrates close to gene promoters in pre-transplant cells and tumors. Moreover, we found that RV preferentially targeted genes encoding for transcription factors, kinases and genomic positions previously described as Common Integration Sites (CIS). CIS are genomic regions targeted at high frequency in tumors by retroviral integrations and probably map within or close to proto-oncogenes activated upon integration. Interestingly, in tumors, RV insertions at CIS and cell cycle genes were further enriched and associated to early lymphomagenesis. Remarkably, LV tested in the same conditions, did not show any tumor acceleration, and targeted CIS much less frequently than RV in pre-transplant cells or tumors, and did not show selection for integrations at any specific gene class. This is the first evidence that prototypic LV have low oncogenic potential, and provides a major rationale for their application to HSC gene therapy. To dissect the role in lymphomagenesis of the strong enhancers in the RV LTRs and the different integration site selection of each vector, we tested an RV with enhancer deleted LTRs (SIN RV) and a moderate promoter in internal position, an LV with a strong RV-like enhancer-promoter into the LTRs or in internal position. Our results show that: SIN RV shows reduced effect on lymphomagenesis acceleration with respect the conventional RV; LV with RV like LTRs treatment significantly accelerates lymphomagenesis, underlining important role of RV-LTRs in oncogenesis; LV with RV-like enhancer in internal position show a reduced genotoxicity. These data show that the type of genetic elements used (strong enhancers or moderate promoter) and their position in the vector genome (LTR or internal positions) significantly influence the vector safety profile. We are currently mapping the integration sites in pre-transplant cells and tumors marked by each vector to identify the genes targeted by the integrations and elucidate the potential mechanism of deregulation. The described model provide an important tool to compare the risk of insertional mutagenesis of different integrating vectors and provides a platform to test different vector types, designs and safety improvements.

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Vonk, Peter Jan, and Robin A. Ohm. "Targeted gene knock-in reduces variation between transformants in the mushroom-forming fungus Schizophyllum commune." Open Research Europe 1 (November 29, 2021): 140. http://dx.doi.org/10.12688/openreseurope.14262.1.

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Gene integration in mushroom-forming fungi currently occurs by the ectopic integration of a plasmid. The locus of integration is unpredictable and, problematically, this generally results in a high variability in gene expression and phenotypes between the transformants. Here, we developed an approach for targeted gene integration (knock-in) in the basidiomycete Schizophyllum commune by replacing a 75-bp non-coding region of the genome with a selection marker and an arbitrary gene of interest using CRISPR-Cas9 ribonucleoproteins. To assess the suitability of our method, we compared targeted integration and ectopic integration of the gene encoding the red fluorescent protein dTomato. Targeted integration resulted in a higher average fluorescence intensity and less variability between the transformants. This method may be applied to any gene construct and may therefore greatly increase the efficiency of functional gene analysis in S. commune.

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Bhattacharyya, Sanchari, Jianmin Tian, Eric E. Bouhassira, and Joseph Locker. "Systematic Targeted Integration to Study Albumin Gene Control Elements." PLoS ONE 6, no. 8 (August 12, 2011): e23234. http://dx.doi.org/10.1371/journal.pone.0023234.

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Moehler, M., S. Schwarz, and A. D. Wagner. "Esophagogastric Cancer: Integration of Targeted Therapies into Systemic Chemotherapy." Current Cancer Drug Targets 11, no. 6 (July 1, 2011): 681–87. http://dx.doi.org/10.2174/156800911796191006.

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Luo, Yuxia, Amy Frederick, John M. Martin, Abraham Scaria, Seng H. Cheng, Donna Armentano, Samuel C. Wadsworth, and Karen A. Vincent. "AAVS1-Targeted Plasmid Integration in AAV Producer Cell Lines." Human Gene Therapy Methods 28, no. 3 (June 2017): 124–38. http://dx.doi.org/10.1089/hgtb.2016.158.

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15

Wilkinson, S. R., and M. Young. "Targeted integration of genes into the Clostridium acetobutylicum chromosome." Microbiology 140, no. 1 (January 1, 1994): 89–95. http://dx.doi.org/10.1099/13500872-140-1-89.

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Shi, Zhaoying, Fengqin Wang, Yan Cui, Zhongzhen Liu, Xiaogang Guo, Yanqi Zhang, Yi Deng, Hui Zhao, and Yonglong Chen. "Heritable CRISPR/Cas9‐mediated targeted integration in Xenopus tropicalis." FASEB Journal 29, no. 12 (August 12, 2015): 4914–23. http://dx.doi.org/10.1096/fj.15-273425.

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Wilkening, Stefan, Saira Afzal, Raffaele Fronza, Christof von Kalle, and Manfred Schmidt. "127. Detection of Vector Integration Sites by Targeted Sequencing." Molecular Therapy 23 (May 2015): S52. http://dx.doi.org/10.1016/s1525-0016(16)33732-7.

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Lee, Keunsub, Alan L. Eggenberger, Raviraj Banakar, Morgan E. McCaw, Huilan Zhu, Marcy Main, Minjeong Kang, Stanton B. Gelvin, and Kan Wang. "CRISPR/Cas9-mediated targeted T-DNA integration in rice." Plant Molecular Biology 99, no. 4-5 (January 15, 2019): 317–28. http://dx.doi.org/10.1007/s11103-018-00819-1.

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Wang, Hongjie, Pavel Sova, Karol Bomsztyk, Qiliang Li, George Stamatoyannopolous, and André Lieber. "Targeted integration of adenovirus vectors in hematopoietic stem cells." Blood Cells, Molecules, and Diseases 40, no. 2 (March 2008): 273–74. http://dx.doi.org/10.1016/j.bcmd.2007.10.056.

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Russel, David W. "Random and targeted integration of adeno-associated virus vectors." Blood Cells, Molecules, and Diseases 40, no. 2 (March 2008): 282–83. http://dx.doi.org/10.1016/j.bcmd.2007.10.073.

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21

Li, Pan, Lijun Zhang, Zhifang Li, Chunlong Xu, Xuguang Du, and Sen Wu. "Cas12a mediates efficient and precise endogenous gene tagging via MITI: microhomology-dependent targeted integrations." Cellular and Molecular Life Sciences 77, no. 19 (December 17, 2019): 3875–84. http://dx.doi.org/10.1007/s00018-019-03396-8.

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AbstractEfficient exogenous DNA integration can be mediated by Cas9 through the non-homology end-joining pathway. However, such integrations are often imprecise and contain a variety of mutations at the junctions between the external DNA and the genomic loci. Here we describe a microhomology-dependent targeted integration method, designated MITI, for precise site-specific gene insertions. We found that the MITI strategy yielded higher knock-in accuracy than Cas9 HITI for the insertion of external DNA and tagging endogenous genes. Furthermore, in combination with negative selection and four different CrRNAs targeting donor vectors and genome-targeted sites with a CrRNA array, MITI facilitated precise ligation at all junctions. Therefore, our Cas12a-based MITI method increases the repertoire of precision genome engineering approaches and provides a useful tool for various gene editing applications.

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Dhingra, Yukti, and Dipali G. Sashital. "A tool for more specific DNA integration." Science 382, no. 6672 (November 17, 2023): 768–69. http://dx.doi.org/10.1126/science.adl0863.

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Agarwal, Arushi, Daryl Pritchard, Alissa Winzeler, Hina Mohammed, Thomas D. Brown, and Gary G. Gustavsen. "Improvements in Clinical Cancer Care Associated with Integration of Personalized Medicine." Journal of Personalized Medicine 14, no. 9 (September 20, 2024): 997. http://dx.doi.org/10.3390/jpm14090997.

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Background: While adoption of personalized medicine (PM) continues to increase in clinical oncology, there is limited data connecting the level of PM adoption at a given institution to improved clinical outcomes for patients. The purpose of this study was to analyze the correlation between health care providers’ scores on a previously described PM integration framework and two outcome measures: the use of targeted therapy and clinical trial enrollment. Methods: This study was conducted using real-world data (RWD) from the Syapse® Learning Health Network (LHN). The PM integration score for six community hospital systems in the LHN was calculated and subsequently correlated with the two outcome measures. Results: Across six institutions, a strong correlation between PM integration score and targeted therapy use was observed in metastatic non-small cell lung cancer (mNSCLC) (R2 = 0.81), an indication with a significant number of approved targeted agents. Conversely, a strong correlation between PM integration score and clinical trial enrollment was observed in metastatic triple-negative breast cancer (TNBC) (R2 = 0.63), an indication with fewer marketed targeted therapies but an active targeted therapy pipeline. Conclusion: The results in these cases suggest that PM integration is a strong indicator of high-quality care practices for both utilization of targeted therapy in more mature PM indications (e.g., mNSCLC) and clinical trial enrollment in more emerging PM indications (e.g., TNBC).

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Brooks, Gabriel A., Linda D. Bosserman, Isa Mambetsariev, and Ravi Salgia. "Value-Based Medicine and Integration of Tumor Biology." American Society of Clinical Oncology Educational Book, no. 37 (May 2017): 833–40. http://dx.doi.org/10.1200/edbk_175519.

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Clinical oncology is in the midst of a genomic revolution, as molecular insights redefine our understanding of cancer biology. Greater awareness of the distinct aberrations that drive carcinogenesis is also contributing to a growing armamentarium of genomically targeted therapies. Although much work remains to better understand how to combine and sequence these therapies, improved outcomes for patients are becoming manifest. As we welcome this genomic revolution in cancer care, oncologists also must grapple with a number of practical problems. Costs of cancer care continue to grow, with targeted therapies responsible for an increasing proportion of spending. Rising costs are bringing the concept of value into sharper focus and challenging the oncology community with implementation of value-based cancer care. This article explores the ways that the genomic revolution is transforming cancer care, describes various frameworks for considering the value of genomically targeted therapies, and outlines key challenges for delivering on the promise of personalized cancer care. It highlights practical solutions for the implementation of value-based care, including investment in biomarker development and clinical trials to improve the efficacy of targeted therapy, the use of evidence-based clinical pathways, team-based care, computerized clinical decision support, and value-based payment approaches.

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Rajca, Lucyna. "The Role of Cities in the Integration of Immigrants in Europe." Studia Europejskie - studies in European Affairs 24, no. 3 (October 20, 2020): 165–81. http://dx.doi.org/10.33067/se.3.2020.9.

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In the era of migration, cities play an important role in integrating immigrants and promoting social cohesion. Sometimes they create and implement integration policies different from these at a national level. The state-run civic integration programs question the thesis of the growing role of cities as these programs have resulted in centralizing integration policies and reducing their role. In recent years, large European cities have been implementing a cultural diversity management model referred to as “intercultural integration”. They have also adopted mainstream policies targeted at the entire population. In terms of immigrant integration policy Polish large cities have recently been following a pattern set by their Western European counterparts. This results from the availability of European funds and trends towards cultural diversity rather than challenges.

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Giordano, Frank A., Stephanie Laufs, Katalin Z. Nagy, Boris Fehse, Agnes Hotz-Wagenblatt, Daniel Lauterborn, Kurt Fellenberg, et al. "Profiling Retroviral Integration Sites in Donor T-Lymphocytes for Suicide Gene Therapy." Blood 104, no. 11 (November 16, 2004): 1744. http://dx.doi.org/10.1182/blood.v104.11.1744.1744.

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Abstract Retroviral vectors encoding the herpes simplex thymidine kinase gene (HSV-Tk) have been employed to render T-lymphocytes (TLCs) sensitive to the prodrug ganciclovir. Such genetically modified T cells have been used for adoptive immunotherapy in the context of allogeneic hematopoietic stem cell transplantation (SCT). Infused T cells have been shown to be susceptible to elimination through exposure to ganciclovir in the event of graft-versus-host disease (GvHD). Recent reports on insertional “genotoxicity” in a mouse gene marking study and a clinical gene therapy trial for X-chromosomal severe combined immunodeficiency (X-SCID) reminded us the actual risk of insertional oncogene activation and subsequent leukemia development. Here we investigated retroviral integration sites in donor TLCs transduced with the MoLV-based TK/neoR vector Mo3TIN of four donors in a clinical HSV-Tk study. A total of 114 retroviral integration sites were detected using highly sensitive and specific ligation-mediated PCR (LM-PCR). 41.2% of all integrations appeared near the transcription start regions (+/−10kb) of genes. Further analysis showed that 57 (50%) of all integrations targeted RefSeq genes. 24 of those appeared in intron 1 (42% of all integrations into genes) while 18% (10/57) of all integrations into genes landed in exon sequences whereas 6 hit the first exon. 18 of the targeted genes (15.8% of all integrations) could be at last assigned to signal transduction pathways, whereas the transcription factor family was afflicted 13 times (11.4% of all integrations). The zinc ion binding group makes up 4 (resp. 6, minding that GTF2HII contains a C2H2 type and KIAA0427 a C-x8-C-x5-C-x3-H-type zinc finger) of them. Among the targeted genes we found integrations into the CD8, CD100, CD44, CX3CR1, HLA-DMP and IL10-receptor genes. Within at a range of 5kb up- and 5kb downstream of vector integrations 15 genes were located that were not hit. 5 are known as transcription factors, whereas two of those are involved in leukemia, namely the homo sapiens myeloid/lymphoid or mixed-lineage leukemia 5 gene (MLL5) and the homo sapiens ALL1 fused gene from 5q31 (AF5Q31). Hit genes are currently examined more systematically in terms of function, e.g. involvement in signal transduction and transcription promoting processes. RISC (Retroviral Insertion estimate of Chromosomal Integration) scores and integration specific data will be submitted to a data warehouse, the collaborative RISC score database (CRSD). Such a systematic data collection similar to the IBMTR or EBMT databases will allow to recognize factors contributing to the safety, optimal transgene expression and persistence of transduced cells in the setting of allogenic matched donor transplantation.

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Giordano, Frank A., Stephanie Laufs, Boris Fehse, K. Zsuzsanna Nagy, Agnes Hotz-Wagenblatt, Daniel Lauterborn, Kurt Fellenberg, et al. "A ComParison of Retroviral Integration Sites in Donor T-Lymphocytes In Vivo and In Vitro." Blood 106, no. 11 (November 16, 2005): 1403. http://dx.doi.org/10.1182/blood.v106.11.1403.1403.

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Abstract Genetically modified T-Lymphocytes (TLCs) have been used for adoptive immunotherapy in the context of allogeneic hematopoietic stem cell transplantation (SCT). Infused TLCs have been shown to be susceptible to elimination through exposure to ganciclovir in the event of graft-versus-host disease (GvHD). Yet, reports on insertional mutagenesis in a mouse gene marking study and a clinical gene therapy trial for X-chromosomal severe combined immunodeficiency (X-SCID) reminded us the actual risk of insertional oncogene activation and subsequent leukemia development. We investigated retroviral integration sites in vitro and in vivo. Therefore, donor TLCs transduced with the MoLV-based TK/neoR vector Mo3TIN for a clinical HSV-Tk study were examined. TLCs of four different donors as well as whole blood samples of two patients transplanted with donor TLCs were analyzed either using highly sensitive and specific ligation-mediated PCR (LM-PCR). A total of 114 retroviral integration sites were detected in vitro. 41.2% of all integrations appeared near the transcription start regions (+/−10kb) of genes. Further analysis showed that 57 (50%) of all integrations targeted RefSeq genes. 24 of those appeared in intron 1 (42% of all integrations into genes) while 18% (10/57) of all integrations into genes landed in exon sequences whereas 6 hit the first exon. 18 of the targeted genes (15.8% of all integrations) could be at last assigned to signal transduction pathways, whereas the transcription factor family was afflicted 13 times (11.4% of all integrations). Among the targeted genes we found integrations into the CD8, CD100, CD44, CX3CR1, HLA-DMP and IL10-receptor genes. Within at a range of 5kb up- and 5kb downstream of vector integrations 15 genes were located that were not hit. 5 are known as transcription factors, whereas two of those are involved in leukemia, namely the homo sapiens myeloid/lymphoid or mixed-lineage leukemia 5 gene (MLL5) and the homo sapiens ALL1 fused gene from 5q31 (AF5Q31). Current analyses are focusing at the in vivo pattern of retroviral integration in DNA of TLCs obtained from transplanted patient’s TLCs. Therefore we developed a new high sensitive PCR method (HS-PCR), an improved LM-PCR to even detect minimal quantities of transduced DNA.

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Cattoglio, Claudia, Giulia Facchini, Daniela Sartori, Antonella Antonelli, Annarita Miccio, Barbara Cassani, Manfred Schmidt, et al. "Hot spots of retroviral integration in human CD34+ hematopoietic cells." Blood 110, no. 6 (September 15, 2007): 1770–78. http://dx.doi.org/10.1182/blood-2007-01-068759.

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Abstract Insertional oncogenesis is a possible consequence of the integration of gamma-retroviral (RV) or lentiviral (LV) vectors into the human genome. RV common insertion sites (CISs) have been identified in hematopoietic malignancies and in the nonmalignant progeny of transduced hematopoietic stem/progenitor cells (HSCs), possibly as a consequence of clonal selection in vivo. We have mapped a large number of RV and LV integrations in human CD34+ HSCs, transduced in vitro and analyzed without selection. Recurrent insertion sites (hot spots) account for more than 21% of the RV integration events, while they are significantly less frequent in the case of LV vectors. RV but not LV hot spots are highly enriched in proto-oncogenes, cancer-associated CISs, and growth-controlling genes, indicating that at least part of the biases observed in the HSC progeny in vivo are characteristics of RV integration, already present in nontransplanted cells. Genes involved in hematopoietic and immune system development are targeted at high frequency and enriched in hot spots, suggesting that the CD34+ gene expression program is instrumental in directing RV integration. The lower propensity of LV vectors for integrating in potentially dangerous regions of the human genome may be a factor determining a better safety profile for gene therapy applications.

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Zhang, Zhongjie, Baolong Niu, Dongfeng Ji, Muwang Li, Kai Li, Anthony A. James, Anjiang Tan, and Yongping Huang. "Silkworm genetic sexing through W chromosome-linked, targeted gene integration." Proceedings of the National Academy of Sciences 115, no. 35 (August 13, 2018): 8752–56. http://dx.doi.org/10.1073/pnas.1810945115.

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Sex separation methods are critical for genetic sexing systems in commercial insect production and sterile insect techniques. Integration of selectable marker genes into a sex chromosome is particularly useful in insects with a heterogametic sex determination system. Here, we describe targeted gene integration of fluorescent marker expression cassettes into a randomly amplified polymorphic DNA (RAPD) marker region in the W chromosome of the lepidopteran model insect Bombyx mori using transcriptional activator-like effector nuclease (TALEN)–mediated genome editing. This silkworm strain shows ubiquitous female-specific red or green fluorescence from the embryonic to adult stages. Furthermore, we developed a binary, female-specific, embryonic lethality system combining the TALEN and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology. This system includes one strain with TALEN-mediated, W-specific Cas9 expression driven by the silkworm germ cell-specific nanos (nos) promoter and another strain with U6-derived single-guide RNA (sgRNA) expression targeting transformer 2 (tra2), an essential gene for silkworm embryonic development. Filial 1 (F1) hybrids exhibit complete female-specific lethality during embryonic stages. Our study provides a promising approach for B. mori genetic sexing and sheds light on developing sterile insect techniques in other insect species, especially in lepidopteran pests with WZ/ZZ sex chromosome systems.

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Mayrhofer, Patrick, Alexander Mader, Bernhard Kratzer, David Reinhart, Willibald Steinfellner, Wolfgang Sommeregger, and Renate Kunert. "Identification of bottlenecks in antibody expression using targeted gene integration." BMC Proceedings 9, Suppl 9 (2015): P7. http://dx.doi.org/10.1186/1753-6561-9-s9-p7.

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Smith, Kevin. "Theoretical mechanisms in targeted and random integration of transgene DNA." Reproduction Nutrition Development 41, no. 6 (November 2001): 465–85. http://dx.doi.org/10.1051/rnd:2001102.

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32

Yao, Xuan, Xing Wang, Xinde Hu, Zhen Liu, Junlai Liu, Haibo Zhou, Xiaowen Shen, et al. "Homology-mediated end joining-based targeted integration using CRISPR/Cas9." Cell Research 27, no. 6 (May 19, 2017): 801–14. http://dx.doi.org/10.1038/cr.2017.76.

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Koch, K. S., T. Aoki, Y. Wang, A. E. Atkinson, A. S. Gleiberman, O. K. Glebov, and H. L. Leffert. "Site-specific integration of targeted DNA into animal cell genomes." Gene 249, no. 1-2 (May 2000): 135–44. http://dx.doi.org/10.1016/s0378-1119(00)00153-0.

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Ward, Peter, and Christopher E. Walsh. "Targeted integration of a rAAV vector into the AAVS1 region." Virology 433, no. 2 (November 2012): 356–66. http://dx.doi.org/10.1016/j.virol.2012.08.015.

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Zou, Tao, Rebecca M. May, and Gary A. Koretzky. "Understanding signal integration through targeted mutations of an adapter protein." FEBS Letters 584, no. 24 (October 20, 2010): 4901–9. http://dx.doi.org/10.1016/j.febslet.2010.10.025.

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Roberts, J. A., I. Miguel-Escalada, K. J. Slovik, K. T. Walsh, Y. Hadzhiev, R. Sanges, E. Stupka, et al. "Targeted transgene integration overcomes variability of position effects in zebrafish." Development 141, no. 3 (January 21, 2014): 715–24. http://dx.doi.org/10.1242/dev.100347.

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Samulski, Richard Jude. "Generation of a Mouse Model for Studying AAV Targeted Integration." Nature Biotechnology 17, S4 (December 1999): 16. http://dx.doi.org/10.1038/70133.

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Siol, Oliver, Moustapha Boutliliss, Thanh Chung, Gernot Glöckner, Theodor Dingermann, and Thomas Winckler. "Role of RNA Polymerase III Transcription Factors in the Selection of Integration Sites by the Dictyostelium Non-Long Terminal Repeat Retrotransposon TRE5-A." Molecular and Cellular Biology 26, no. 22 (September 18, 2006): 8242–51. http://dx.doi.org/10.1128/mcb.01348-06.

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ABSTRACT In the compact Dictyostelium discoideum genome, non-long terminal repeat (non-LTR) retrotransposons known as TREs avoid accidental integration-mediated gene disruption by targeting the vicinity of tRNA genes. In this study we provide the first evidence that proteins of a non-LTR retrotransposon interact with a target-specific transcription factor to direct its integration. We applied an in vivo selection system that allows for the isolation of natural TRE5-A integrations into a known genomic location upstream of tRNA genes. TRE5-A frequently modified the integration site in a way characteristic of other non-LTR retrotransposons by adding nontemplated extra nucleotides and generating small and extended target site deletions. Mutations within the B-box promoter of the targeted tRNA genes interfered with both the in vitro binding of RNA polymerase III transcription factor TFIIIC and the ability of TRE5-A to target these genes. An isolated B box was sufficient to enhance TRE5-A integration in the absence of a surrounding tRNA gene. The RNA polymerase III-transcribed ribosomal 5S gene recruits TFIIIC in a B-box-independent manner, yet it was readily targeted by TRE5-A in our assay. These results suggest a direct role of an RNA polymerase III transcription factor in the targeting process.

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Marchetti, Philippe, Pierre Guerreschi, Laurent Mortier, and Jerome Kluza. "Integration of Mitochondrial Targeting for Molecular Cancer Therapeutics." International Journal of Cell Biology 2015 (2015): 1–17. http://dx.doi.org/10.1155/2015/283145.

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Mitochondrial metabolism greatly influences cancer cell survival, invasion, metastasis, and resistance to many anticancer drugs. Furthermore, molecular-targeted therapies (e.g., oncogenic kinase inhibitors) create a dependence of surviving cells on mitochondrial metabolism. For these reasons, inhibition of mitochondrial metabolism represents promising therapeutic pathways in cancer. This review provides an overview of mitochondrial metabolism in cancer and discusses the limitations of mitochondrial inhibition for cancer treatment. Finally, we present preclinical evidence that mitochondrial inhibition could be associated with oncogenic “drivers” inhibitors, which may lead to innovative drug combinations for improving the efficacy of molecular-targeted therapy.

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Cheng, Luying, Xiaohan Zhang, and Ziming Xu. "Exploring Dimensions in Digital Economy and Manufacturing Integration: Analyzing with DEA-Malmquist Model and Emphasizing the Role of ERP Systems in Enhancing Collaboration and Efficiency." Journal of Information Systems Engineering and Management 8, no. 1 (January 27, 2023): 25092. http://dx.doi.org/10.55267/iadt.07.14080.

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ERP integration influenced digital economy manufacturing in this study. The DEA-Malmquist method calculated the digital economy manufacturing integration contribution rate index. In China, the researchers targeted Beijing-Tianjin-Hebei, Greater Bay Area, and Changzhu Lake. Regional economic growth rose with manufacturing integration. Integration accelerates commerce, resource allocation, regional manufacturing, and digital economy growth. Integration boosts corporate and customer service accessibility, reports say. These regions experienced increasing client demand and innovation. Integration's diverse impact on economic growth differed by location due to economic structures and stages. To understand how digital economy and industrial integration maintain economic growth, ERP digitalization, government policies, digital infrastructure, and market rules must be investigated. The DEA-Malmquist regional digital economy manufacturing integrated latitude measurement model is crucial. The model and research benefit government and business strategy. This study boosts sector growth and long-term economic and industrial development by raising knowledge of regional digital economies and manufacturing integration.

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Evans, Maggie C., and Greg M. Anderson. "Neuroendocrine integration of nutritional signals on reproduction." Journal of Molecular Endocrinology 58, no. 2 (February 2017): R107—R128. http://dx.doi.org/10.1530/jme-16-0212.

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Reproductive function in mammals is energetically costly and therefore tightly regulated by nutritional status. To enable this integration of metabolic and reproductive function, information regarding peripheral nutritional status must be relayed centrally to the gonadotropin-releasing hormone (GNRH) neurons that drive reproductive function. The metabolically relevant hormones leptin, insulin and ghrelin have been identified as key mediators of this ‘metabolic control of fertility’. However, the neural circuitry through which they act to exert their control over GNRH drive remains incompletely understood. With the advent of Cre-LoxP technology, it has become possible to perform targeted gene-deletion and gene-rescue experiments and thus test the functional requirement and sufficiency, respectively, of discrete hormone–neuron signaling pathways in the metabolic control of reproductive function. This review discusses the findings from these investigations, and attempts to put them in context with what is known from clinical situations and wild-type animal models. What emerges from this discussion is clear evidence that the integration of nutritional signals on reproduction is complex and highly redundant, and therefore, surprisingly difficult to perturb. Consequently, the deletion of individual hormone–neuron signaling pathways often fails to cause reproductive phenotypes, despite strong evidence that the targeted pathway plays a role under normal physiological conditions. Although transgenic studies rarely reveal a critical role for discrete signaling pathways, they nevertheless prove to be a good strategy for identifying whether a targeted pathway is absolutely required, critically involved, sufficient or dispensable in the metabolic control of fertility.

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Dong, Oliver Xiaoou, and Pamela C. Ronald. "Targeted DNA insertion in plants." Proceedings of the National Academy of Sciences 118, no. 22 (April 30, 2021): e2004834117. http://dx.doi.org/10.1073/pnas.2004834117.

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Conventional methods of DNA sequence insertion into plants, using Agrobacterium-mediated transformation or microprojectile bombardment, result in the integration of the DNA at random sites in the genome. These plants may exhibit altered agronomic traits as a consequence of disruption or silencing of genes that serve a critical function. Also, genes of interest inserted at random sites are often not expressed at the desired level. For these reasons, targeted DNA insertion at suitable genomic sites in plants is a desirable alternative. In this paper we review approaches of targeted DNA insertion in plant genomes, discuss current technical challenges, and describe promising applications of targeted DNA insertion for crop genetic improvement.

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Keeney, J. B., and J. D. Boeke. "Efficient targeted integration at leu1-32 and ura4-294 in Schizosaccharomyces pombe." Genetics 136, no. 3 (March 1, 1994): 849–56. http://dx.doi.org/10.1093/genetics/136.3.849.

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Abstract Homologous integration into the fission yeast Schizosaccharomyces pombe has not been well characterized. In this study, we have examined integration of plasmids carrying the leu1+ and ura4+ genes into their chromosomal loci. Genomic DNA blot analysis demonstrated that the majority of transformants have one or more copies of the plasmid vector integrated via homologous recombination with a much smaller fraction of gene conversion to leu1+ or ura4+. Non-homologous recombination events were not observed for either gene. We describe the construction of generally useful leu1+ and ura4+ plasmids for targeted integration at the leu1-32 and ura4-294 loci of S. pombe.

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Lederman, Susan J., Roberta L. Klatzky, and Catherine L. Reed. "Constraints on Haptic Integration of Spatially Shared Object Dimensions." Perception 22, no. 6 (June 1993): 723–43. http://dx.doi.org/10.1068/p220723.

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A study of the haptic integration of texture, shape, and hardness of nonplanar solid objects is reported. In experiment 1 the relative discriminability of the objects along each dimension was assessed. While levels of texture and shape were equally discriminable, hardness discriminations proved considerably more difficult. The extent of dimensional integration in a speeded classification task when both dimensions could be extracted from the same local patch was investigated in experiments 2 and 3. In experiment 2 subjects were initially encouraged to attend to a nontargeted dimension covarying with a targeted one. The nontargeted dimension was subsequently held constant (withdrawn). In experiment 3 dimensional variation was introduced which was uncorrelated with the targeted property during the course of categorization and hence discouraged subjects from attending to the nontargeted property. The results of these two studies converged in showing evidence of bidirectional dimensional integration between texture and shape and unidirectional integration when hardness was the targeted dimension. The failure to integrate hardness into categorization based on texture or shape was attributed to the difficulty of hardness discriminations. Integration effects in experiment 3 were not consistently smaller than those in experiment 2, which suggests a strong involuntary component to dimensional integration. The results of an analysis of the accompanying hand movements are interpreted in terms of constraints on dimensional integration. Implications for visual, cross-modal, and two-handed codimensional processing are also discussed.

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Giosa, Domenico, Daniele Lombardo, Cristina Musolino, Valeria Chines, Giuseppina Raffa, Deborah D’aliberti, Francesca Casuscelli di Tocco, et al. "A high-throughput viral integration sequencing method reveals that mitochondrial DNA is frequently targeted by HBV integration." Journal of Hepatology 77 (July 2022): S259. http://dx.doi.org/10.1016/s0168-8278(22)00889-3.

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Zhang, Meng, Che Yang, Ipek Tasan, and Huimin Zhao. "Expanding the Potential of Mammalian Genome Engineering via Targeted DNA Integration." ACS Synthetic Biology 10, no. 3 (February 17, 2021): 429–46. http://dx.doi.org/10.1021/acssynbio.0c00576.

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Cui, Xiaoxia, Diana Ji, Daniel A. Fisher, Yumei Wu, David M. Briner, and Edward J. Weinstein. "Targeted integration in rat and mouse embryos with zinc-finger nucleases." Nature Biotechnology 29, no. 1 (January 2011): 64–67. http://dx.doi.org/10.1038/nbt.1731.

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Feng, Xiaofeng, Amy L. Bednarz, and Sean D. Colloms. "Precise targeted integration by a chimaeric transposase zinc-finger fusion protein." Nucleic Acids Research 38, no. 4 (December 3, 2009): 1204–16. http://dx.doi.org/10.1093/nar/gkp1068.

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Correia, Antonio, Juan F. Martin, and Jose M. Castro. "Targeted integration of foreign genes into repetitive sequences of theBrevibacterium lactofermentumchromosome." FEMS Microbiology Letters 142, no. 2-3 (September 1996): 259–64. http://dx.doi.org/10.1111/j.1574-6968.1996.tb08440.x.

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Wilkening, Stefan, Saira Afzal, Elena Senís, Raffaele Fronza, Christof von Kalle, Dirk Grimm, and Manfred Schmidt. "470. New Insights into rAAV Integration Mechanisms by Targeted Enrichment Sequencing." Molecular Therapy 24 (May 2016): S186. http://dx.doi.org/10.1016/s1525-0016(16)33279-8.

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Journal articles on the topic 'Targeted integration'

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