Targeting a retroviral vector in the absence of a known cell-targeting ligand

被引:34
作者
Bupp, K [1 ]
Roth, MJ [1 ]
机构
[1] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Biochem, Piscataway, NJ 08854 USA
关键词
D O I
10.1089/104303403322495061
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
An important requirement for many gene therapy applications is to direct therapeutic genes specifically to target cells. Here we describe an improved vector targeting method that does not depend on the use of a known cell-targeting ligand. It entails screening a library of constitutively produced retroviruses with random amino acid substitutions in the cell-targeting region of the envelope proteins for their ability to mediate gene delivery to a target cell. By screening such a library on the ras-transformed 143B human cell line, we have isolated an envelope protein that preferentially targets 143B cells and 293T cells expressing the SV40 T antigen via a novel, unidentified receptor. Furthermore, retroviruses expressing the library-derived envelope protein can be concentrated by centrifugation. This is the first demonstration of a novel concept in vector targeting: the selection of productive retroviral entry via an alternate receptor with modified cellular tropism in the absence of a known cell-targeting moiety. The method is, in principle, applicable even to cells that have not been well characterized, and therefore potentially suitable for targeting many diverse cell types.
引用
收藏
页码:1557 / 1564
页数:8
相关论文
共 44 条
[1]  
ALTSCHUL SF, 1990, J MOL BIOL, V215, P403, DOI 10.1006/jmbi.1990.9999
[2]   Targeting retroviral vectors to CD34-expressing cells: Binding to CD34 does not catalyze virus-cell fusion [J].
Benedict, CA ;
Tun, RYM ;
Rubinstein, DB ;
Guillaume, T ;
Cannon, PM ;
Anderson, WF .
HUMAN GENE THERAPY, 1999, 10 (04) :545-557
[3]   Three distinct envelope domains, variably present in subgroup B feline leukemia virus recombinants, mediate Pit1 and Pit2 receptor recognition [J].
Boomer, S ;
Eiden, M ;
Burns, CC ;
Overbaugh, J .
JOURNAL OF VIROLOGY, 1997, 71 (11) :8116-8123
[4]   Altering retroviral tropism using a random-display envelope library [J].
Bupp, K ;
Roth, MJ .
MOLECULAR THERAPY, 2002, 5 (03) :329-335
[5]  
Bupp K, 2000, VIRAL VECTORS, P379
[6]   SELECTIVE ASSAY FOR HERPES-SIMPLEX VIRUSES EXPRESSING THYMIDINE KINASE [J].
CAMPIONEPICCARDO, J ;
RAWLS, WE ;
BACCHETTI, S .
JOURNAL OF VIROLOGY, 1979, 31 (02) :281-287
[7]   DIFFERENT MURINE CELL-LINES MANIFEST UNIQUE PATTERNS OF INTERFERENCE TO SUPERINFECTION BY MURINE LEUKEMIA VIRUSES [J].
CHESEBRO, B ;
WEHRLY, K .
VIROLOGY, 1985, 141 (01) :119-129
[8]   HIGH-TITER PACKAGING CELLS PRODUCING RECOMBINANT RETROVIRUSES RESISTANT TO HUMAN SERUM [J].
COSSET, FL ;
TAKEUCHI, Y ;
BATTINI, JL ;
WEISS, RA ;
COLLINS, MKL .
JOURNAL OF VIROLOGY, 1995, 69 (12) :7430-7436
[9]   RETROVIRAL RETARGETING BY ENVELOPES EXPRESSING AN N-TERMINAL BINDING DOMAIN [J].
COSSET, FL ;
MORLING, FJ ;
TAKEUCHI, Y ;
WEISS, RA ;
COLLINS, MKL ;
RUSSELL, SJ .
JOURNAL OF VIROLOGY, 1995, 69 (10) :6314-6322
[10]  
Dachs GU, 1997, ONCOL RES, V9, P313