Retrovirus molecular conjugates. A novel, high transduction efficiency, potentially safety-improved, gene transfer system

The Journal of Biological Chemistry
Q ZhongPaul Schwarzenberger

Abstract

Two significant barriers limit the use of amphotropic retrovirus for human gene transfer protocols: 1) low transduction efficiency in cells with low receptor expression and 2) safety concerns originating from the risk of formation and propagation of replication competent virus in vivo. In principle, if ecotropic retrovirus, which is incapable of infecting human cells, could be transiently modified to effectively transduce human cells, this safety risk could be alleviated. Here we demonstrate that formation of amphotropic retrovirus polylysine molecular conjugates (aMMLV-PL) enhanced gene transfer up to 10-fold in a variety of human cell lines over the equivalent of unconjugated vector (aMMLV). The polylysine modification and formation of ecotropic retrovirus molecular conjugates (eMMLV-PL) permitted effective and stable transduction of different human cell lines as well as primary human bone marrow stroma cells at frequencies of greater than 80%. It is conceivable that this novel ecotropic-based conjugate retrovirus vector could also potentially provide enhanced safety characteristics not only over amphotropic retrovirus vectors but also over genetically tropism-modified recombinant ecotropic vectors. In contrast to genetic mod...Continue Reading

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Citations

May 14, 2005·Cancer Gene Therapy·Weitao HuangPaul Schwarzenberger
May 16, 2008·Human Gene Therapy·Minna U KaikkonenKari J Airenne
Mar 18, 2010·Expert Opinion on Drug Delivery·Hanna P LeschSeppo Ylä-Herttuala
Sep 6, 2003·The Journal of Pharmacy and Pharmacology·Thomas P JohnstonAshim K Mitra

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