Vector integration: Location, location, location

Mok, Hoi Ping; Lever, Andrew

doi:10.1038/sj.gt.3302415

Cited by 4 publications

(2 citation statements)

References 23 publications

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“…One might, however, argue that, since all the retroviral sequences mentioned so far are GC-rich [31], integration into GC-rich isochores could depend upon the requirement for a compositional match between the retroviral sequence and the isochores of the host genome without being related to chromatin “openness”. Integration into GC-rich isochores was also found, however, for exogenous Mouse Mammary Tumor Virus (MMTV; [32]) and Human Immunodeficiency Virus (HIV-I; [6], [33]–[36]) which are GC-poor. This obviously favors the idea of an integration into open chromatin structures.…”

Section: Discussionmentioning

confidence: 99%

Mapping Insertions, Deletions and SNPs on Venter's Chromosomes

Costantini

Bernardi

2009

PLoS ONE

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BackgroundThe very recent availability of fully sequenced individual human genomes is a major revolution in biology which is certainly going to provide new insights into genetic diseases and genomic rearrangements.ResultsWe mapped the insertions, deletions and SNPs (single nucleotide polymorphisms) that are present in Craig Venter's genome, more precisely on chromosomes 17 to 22, and compared them with the human reference genome hg17. Our results show that insertions and deletions are almost absent in L1 and generally scarce in L2 isochore families (GC-poor L1+L2 isochores represent slightly over half of the human genome), whereas they increase in GC-rich isochores, largely paralleling the densities of genes, retroviral integrations and Alu sequences. The distributions of insertions/deletions are in striking contrast with those of SNPs which exhibit almost the same density across all isochore families with, however, a trend for lower concentrations in gene-rich regions.ConclusionsOur study strongly suggests that the distribution of insertions/deletions is due to the structure of chromatin which is mostly open in gene-rich, GC-rich isochores, and largely closed in gene-poor, GC-poor isochores. The different distributions of insertions/deletions and SNPs are clearly related to the two different responsible mechanisms, namely recombination and point mutations.

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Section: Discussionmentioning

confidence: 99%

Mapping Insertions, Deletions and SNPs on Venter's Chromosomes

Costantini

Bernardi

2009

PLoS ONE

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“…The short half-life ( t 1/2 ∼1.5 min) of siRNA in blood and need for intracellular delivery are challenges for translation to the clinic. A variety of methods have been developed to deliver siRNA, including direct intravenous injection of “naked” or chemically stabilized siRNA, , packaging of siRNA into DNA plasmid vectors, , transposon vectors (transgenic plasmids), plasmid-infected viruses, virosomes (reconstituted viral envelopes), lentiviral vectors, , and liposomes . We have previously demonstrated that pH-responsive liposomes are advantageous for delivering siRNA, because they not only improve pharmacokinetics but also provide a stable shield from enzyme degradation …”

Section: Introductionmentioning

confidence: 99%

Inhibiting Metastatic Breast Cancer Cell Migration via the Synergy of Targeted, pH-triggered siRNA Delivery and Chemokine Axis Blockade

et al. 2014

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Because breast cancer patient survival inversely correlates with metastasis, we engineered vehicles to inhibit both the C-X-C chemokine receptor type 4 (CXCR4) and lipocalin-2 (Lcn2) mediated migratory pathways. pH-responsive liposomes were designed to protect and trigger the release of Lcn2 siRNA. Liposomes were modified with anti-CXCR4 antibodies to target metastatic breast cancer (MBC) cells and block migration along the CXCR4-CXCL12 axis. This synergistic approach—coupling the CXCR4 axis blockade with Lcn2 silencing—significantly reduced migration in triple-negative human breast cancer cells (88% for MDA-MB-436 and 92% for MDA-MB-231). The results suggested that drug delivery vehicles engineered to attack multiple migratory pathways may effectively slow progression of MBC.

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A strategy for systemic delivery of the oncolytic herpes virus HSV1716: redirected tropism by antibody-binding sites incorporated on the virion surface as a glycoprotein D fusion protein

2008

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We report on the ability of single-chain variable fragment (scFv) incorporated into the viral envelope to alter the tropism of herpes simplex virus (HSV) 1716. Using recombinant viruses expressing fusion proteins comprising cellsurface antigen-specific scFvs N terminus linked to amino acids 274-393 of gD, we demonstrated that the tropism of these HSV1716 variants was modified such that infection was mediated by the cognate antigen. Thus, an HSV1716 variant that expressed an anti-CD55 scFv targeting moiety linked to these gD residues was able to infect non-permissive Chinese hamster ovary cells expressing CD55 and this infection was specifically blocked by an anti-CD55 monoclonal antibody. Similarly, the infection efficiency of an HSV1716 variant for semi-permissive human leukaemic, CD38-positive cell lines was greatly improved by an anti-CD38 scFv targeting moiety linked to gD residues 274-393, and this enhanced infectivity was abrogated specifically by an anti-CD38 monoclonal antibody. Finally, intravenous/ intraperitoneal injection of an HSV1716 variant displaying an anti-epidermal growth factor receptor (EGFR) scFv linked to residues 274-393 of gD enhanced destruction of subcutaneous EGFR-positive tumours in nude mice compared to unmodified HSV1716. Therefore, targeting of HSV1716 oncolysis to specific cell types through the display of entry mediating scFv/gD fusion proteins represents an efficient route for systemic delivery.

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Vector integration: Location, location, location

Abstract: A new analysis of vector integration has shown how integration site varies among three different groups of retroviruses 1

Cited by 4 publications

References 23 publications

Mapping Insertions, Deletions and SNPs on Venter's Chromosomes

Mapping Insertions, Deletions and SNPs on Venter's Chromosomes

Inhibiting Metastatic Breast Cancer Cell Migration via the Synergy of Targeted, pH-triggered siRNA Delivery and Chemokine Axis Blockade

A strategy for systemic delivery of the oncolytic herpes virus HSV1716: redirected tropism by antibody-binding sites incorporated on the virion surface as a glycoprotein D fusion protein

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