Retrovirus Molecular Conjugates
A NOVEL, HIGH TRANSDUCTION EFFICIENCY, POTENTIALLY
SAFETY-IMPROVED, GENE TRANSFER SYSTEM*
Qiu
Zhong
§,
Jay K.
Kolls¶, and
Paul
Schwarzenberger§
From the Gene Therapy Program,
§ Department of Medicine, and ¶ Department of
Pediatrics, Louisiana State University Health Sciences Center,
New Orleans, Louisianna 70122
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
modifications, physical or chemical modifications are not propagated.
Thus, formation of replication competent eMMLV from conjugates would be
self-limited and would not result in virus propagation in humans.
*
This work was supported by Leukemia Society of America
Translational Research Award 6191 (to P. S.) and by National
Institutes of Health Grant R01 CA81125-01 (to P. S.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Gene Therapy
Program, LSUHSC, 533 Bolivar St., Rm. 611 New Orleans, LA 70122. Tel.:
504-568-5843; Fax: 504-568-8500; E-mail: pschwa1@lsuhsc.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
