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Targeting of retroviral vectors through protease-substrate interactions

Nilson, B H LU ; Morling, F J; Cosset, F L and Russell, S J (1996) In Gene Therapy 3(4). p.280-286
Abstract

Targetable, injectable vectors would greatly facilitate the development of in vivo therapy strategies. Viral and nonviral vectors can be targeted through ligand-receptor interactions, but protease-substrate interactions have not previously been exploited for vector targeting. Epidermal growth factor (EGF) was fused to a retroviral envelope glycoprotein via a cleavable linker comprising a factor Xa protease recognition signal. Vector particles displaying the cleavable EGF domain could bind to EGF receptors on human cells but did not transfer their genes until they were cleaved by factor Xa protease, whereupon gene delivery proceeded normally. Proteolytic activation of receptor-targeted vectors can therefore provide the basis for a novel... (More)

Targetable, injectable vectors would greatly facilitate the development of in vivo therapy strategies. Viral and nonviral vectors can be targeted through ligand-receptor interactions, but protease-substrate interactions have not previously been exploited for vector targeting. Epidermal growth factor (EGF) was fused to a retroviral envelope glycoprotein via a cleavable linker comprising a factor Xa protease recognition signal. Vector particles displaying the cleavable EGF domain could bind to EGF receptors on human cells but did not transfer their genes until they were cleaved by factor Xa protease, whereupon gene delivery proceeded normally. Proteolytic activation of receptor-targeted vectors can therefore provide the basis for a novel two-step targeting strategy that may facilitate efficient targeted in vivo delivery of therapeutic genes.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
3T3 Cells, Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Cell Line, DNA, Recombinant, Endopeptidases, Epidermal Growth Factor, Factor Xa, Gene Products, env, Gene Targeting, Genetic Therapy, Genetic Vectors, Humans, Ligands, Mice, Molecular Sequence Data, Recombinant Fusion Proteins, Retroviridae, Substrate Specificity, Journal Article, Research Support, Non-U.S. Gov't
in
Gene Therapy
volume
3
issue
4
pages
280 - 286
publisher
Nature Publishing Group
external identifiers
  • scopus:0029917238
ISSN
0969-7128
language
English
LU publication?
no
id
df99263e-abf3-4c64-93ec-87a9bcd9ace1
date added to LUP
2018-05-26 13:54:56
date last changed
2018-06-03 05:07:03
@article{df99263e-abf3-4c64-93ec-87a9bcd9ace1,
  abstract     = {<p>Targetable, injectable vectors would greatly facilitate the development of in vivo therapy strategies. Viral and nonviral vectors can be targeted through ligand-receptor interactions, but protease-substrate interactions have not previously been exploited for vector targeting. Epidermal growth factor (EGF) was fused to a retroviral envelope glycoprotein via a cleavable linker comprising a factor Xa protease recognition signal. Vector particles displaying the cleavable EGF domain could bind to EGF receptors on human cells but did not transfer their genes until they were cleaved by factor Xa protease, whereupon gene delivery proceeded normally. Proteolytic activation of receptor-targeted vectors can therefore provide the basis for a novel two-step targeting strategy that may facilitate efficient targeted in vivo delivery of therapeutic genes.</p>},
  author       = {Nilson, B H and Morling, F J and Cosset, F L and Russell, S J},
  issn         = {0969-7128},
  keyword      = {3T3 Cells,Amino Acid Sequence,Animals,Base Sequence,Binding Sites,Cell Line,DNA, Recombinant,Endopeptidases,Epidermal Growth Factor,Factor Xa,Gene Products, env,Gene Targeting,Genetic Therapy,Genetic Vectors,Humans,Ligands,Mice,Molecular Sequence Data,Recombinant Fusion Proteins,Retroviridae,Substrate Specificity,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {4},
  pages        = {280--286},
  publisher    = {Nature Publishing Group},
  series       = {Gene Therapy},
  title        = {Targeting of retroviral vectors through protease-substrate interactions},
  volume       = {3},
  year         = {1996},
}