Enhanced in vivo gene transfer into the placenta using RGD fiber-mutant adenovirus vector
Source abstract
Abstract
Among viral vectors, the fiber-mutant adenovirus vector carrying the Arg-Gly-Asp (RGD) peptide sequence (Ad-RGD) seems to have potential for both clinical gene therapy and basic research. As a part of a thorough evaluation of Ad-RGD in preclinical studies, we designed an experiment to investigate in detail the distribution of Ad-RGD compared with conventional adenovirus vector (WT-Ad) in pregnant mice. Surprisingly, Ad-RGD had substantial placental tropism, at 10-100 times that of WT-Ad. Transgene expression was sustained for at least 7 days, and Ad-RGD expressing firefly luciferase or red fluorescent protein has so far caused no placental dysfunction leading to fetal death. Ad-RGD showed high levels of transduction efficiency in in vitro-differentiated trophoblast stem cells, in which higher expression of αvβ3 integrin than in undifferentiated cells was observed. Our results suggest that the use of Ad-RGD or another RGD-mediated targeting strategy holds promise for drug delivery to the placenta.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Virus-based gene therapy research · RNA Interference and Gene Delivery · CAR-T cell therapy research
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (52)
Show source-provided references
1. Adenoviral gene therapy10.1634/theoncologist.7-1-46 ↗
2. Adenovirus vectors composed of subgroup B adenoviruses10.2174/156652307781369137 ↗
3. Approaches to improving the kinetics of adenovirus-delivered genes and gene products10.1016/j.addr.2004.12.010 ↗
4. Adenovirus serotype 35 vector-mediated transduction following direct administration into organs of nonhuman primates10.1038/gt.2008.154 ↗
5. Modification of pIX or hexon based on fiberless Ad vectors is not effective for targeted Ad vectors10.1016/j.jconrel.2007.12.016 ↗
6. miR-122a-regulated expression of a suicide gene prevents hepatotoxicity without altering antitumor effects in suicide gene therapy10.1038/mt.2008.159 ↗
7. A simplified system for constructing recombinant adenoviral vectors containing heterologous peptides in the HI loop of their fiber knob10.1038/sj.gt.3301453 ↗
8. CAR- or alphav integrin-binding ablated adenovirus vectors, but not fiber-modified vectors containing RGD peptide, do not change the systemic gene transfer properties in mice10.1038/sj.gt.3301701 ↗
9. An adenovirus vector with genetically modified fibers demonstrates expanded tropism via utilization of a coxsackievirus and adenovirus receptor-independent cell entry mechanism10.1128/JVI.72.12.9706-9713.1998 ↗
10. Efficient antigen gene transduction using Arg-Gly-Asp fiber-mutant adenovirus vectors can potentiate antitumor vaccine efficacy and maturation of murine dendritic cells
11. A novel PPAR gamma gene therapy to control inflammation associated with inflammatory bowel disease in a murine model10.1016/S0016-5085(03)00262-2 ↗
12. An investigation of adverse effects caused by the injection of high-dose TNFalpha-expressing adenovirus vector into established murine melanoma10.1038/sj.gt.3301876 ↗
13. Efficient construction of a recombinant adenovirus vector by an improved in vitro ligation method10.1089/hum.1998.9.17-2577 ↗
14. A simple method for constructing E1- and E1/E4-deleted recombinant adenoviral vectors10.1089/10430349950017374 ↗
15. A simple and efficient method for purification of infectious recombinant adenovirus10.7883/yoken1952.47.157 ↗
16. ‘Green mice’ as a source of ubiquitous green cells10.1016/S0014-5793(97)00313-X ↗
17. Trialkyltin compounds bind retinoid X receptor to alter human placental endocrine functions10.1210/me.2004-0397 ↗
18. Promotion of trophoblast stem cell proliferation by FGF410.1126/science.282.5396.2072 ↗
19. Retinoic acid promotes differentiation of trophoblast stem cells to a giant cell fate10.1006/dbio.2001.0300 ↗
20. Strain related variations in adenovirally mediated transgene expression from mouse hepatocytes in vivo: comparisons between immunocompetent and immunodeficient inbred strains
21. Influence of coagulation factor x on in vitro and in vivo gene delivery by adenovirus (Ad) 5, Ad35, and chimeric Ad5/Ad35 vectors10.1038/mt.2009.152 ↗
22. Efficient incorporation of a functional hyper-stable single-chain antibody fragment protein-IX fusion in the adenovirus capsid10.1038/sj.gt.3302908 ↗
23. Selective targeting of gene transfer to vascular endothelial cells by use of peptides isolated by phage display10.1161/01.CIR.102.2.231 ↗
24. Ablating adenovirus type 5 fiber-CAR binding and HI loop insertion of the SIGYPLP peptide generate an endothelial cell-selective adenovirus10.1006/mthe.2001.0489 ↗
25. Recombinant human adenovirus: targeting to the human transferrin receptor improves gene transfer to brain microcapillary endothelium10.1128/JVI.74.23.11359-11366.2000 ↗
26. Development of efficient viral vectors selective for vascular smooth muscle cells10.1016/j.ymthe.2003.11.006 ↗
27. Development of renal-targeted vectors through combined in vivo phage display and capsid engineering of adenoviral fibers from serotype 19p10.1038/sj.mt.6300214 ↗
28. Serotype chimeric and fiber-mutated adenovirus Ad5/19p-HIT for targeting renal cancer and untargeting the liver10.1089/hum.2008.108 ↗
29. Retargeting of adenovirus vectors through genetic fusion of a single-chain or single-domain antibody to capsid protein IX10.1128/JVI.02665-09 ↗
30. Targeting of synthetic gene delivery systems
31. Increased in vitro and in vivo gene transfer by adenovirus vectors containing chimeric fiber proteins10.1128/jvi.71.11.8221-8229.1997 ↗
32. CAR-dependent and CAR-independent pathways of adenovirus vector-mediated gene transfer and expression in human fibroblasts10.1172/JCI5309 ↗
33. Improved adenovirus vectors for infection of cardiovascular tissues10.1128/JVI.75.7.3335-3342.2001 ↗
34. Highly efficient transduction of human monocyte-derived dendritic cells with subgroup B fiber-modified adenovirus vectors enhances transgene-encoded antigen presentation to cytotoxic T cells10.4049/jimmunol.166.8.5236 ↗
35. Adenovirus type 5 and 7 capsid chimera: fiber replacement alters receptor tropism without affecting primary immune neutralization epitopes10.1128/jvi.70.4.2116-2123.1996 ↗
36. Selective targeting of human cells by a chimeric adenovirus vector containing a modified fiber protein10.1128/jvi.71.6.4782-4790.1997 ↗
37. Group D adenoviruses infect primary central nervous system cells more efficiently than those from group C10.1128/JVI.73.3.2537-2540.1999 ↗
38. The influence of synovial fluid on adenovirus-mediated gene transfer to the synovial tissue10.1002/1529-0131(200101)44:1<48::AID-ANR7>3.0.CO;2-D ↗
39. A capsid-modified adenovirus vector devoid of all viral genes: assessment of transduction and toxicity in human hematopoietic cells10.1006/mthe.2000.0410 ↗
40. Adenovirus type 5 p.eudotyped with adenovirus type 37 fiber uses sialic acid as a cellular receptor10.1016/j.virol.2004.04.001 ↗
41. A chimeric adenovirus vector encoding reovirus attachment protein sigma1 targets cells expressing junctional adhesion molecule 110.1073/pnas.0400542101 ↗
42. In vitro dendritic cell infection by pseudotyped adenoviral vectors does not correlate with their in vivo immunogenicity10.1016/j.virol.2004.11.014 ↗
43. Placental gene transfer: transgene screening in mice for trophic effects on the placenta
44. Angiographically guided utero-placental gene transfer in rabbits with adenoviruses, plasmid/liposomes and plasmid/polyethyleneimine complexes10.1038/sj.gt.3301444 ↗
45. Comparative in vivo approaches for selective adenovirus-mediated gene delivery to the placenta10.1089/10430340050016247 ↗
46. In utero cardiac gene transfer via intraplacental delivery of recombinant adenovirus10.1161/01.CIR.96.10.3561 ↗
47. Rhesus monkey placental transgene expression after lentiviral gene transfer into preimplantation embryos10.1073/pnas.181336098 ↗
48. Complementation of placental defects and embryonic lethality by trophoblast-specific lentiviral gene transfer10.1038/nbt1280 ↗
49. Biodistribution and retargeting of FX-binding ablated adenovirus serotype 5 vectors10.1182/blood-2009-12-260026 ↗
50. Adenoviral expression of suppressor of cytokine signaling-1 reduces adenovirus vector-induced innate immune responses10.4049/jimmunol.180.7.4931 ↗
51. Development of fiber-substituted adenovirus vectors containing foreign peptides in the adenovirus serotype 35 fiber knob10.1038/gt.2009.65 ↗
52. Molecular cloning of a murine homologue of membrane cofactor protein (CD46): preferential expression in testicular germ cells10.1042/bj3300163 ↗