Dual-target inhibition of HIV-1 in vitro by means of an adeno-associated virus antisense vector.
An adeno-associated virus vector encoding an antisense RNA was used to transduce stable intracellular resistance to human immunodeficiency virus-1 (HIV-1) in human hemopoietic and non-hemopoietic cell lines. The antisense targets are present in all HIV-1 transcripts and include the TAR sequence, which is critical for transcription and virus replication, and the polyadenylation signal. Cell lines expressing antisense RNA showed up to 95 percent inhibition of gene expression directed by the HIV-1 long terminal repeat and greater than 99 percent reduction in infectious HIV-1 production, with no detectable cellular toxicity. Because of their efficient transcription and inability to recombine with HIV-1, adeno-associated virus vectors represent a promising form of anti-retroviral gene therapy.
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Rockville, MD 20852.
S
S
Chatterjee
P R
PR
Johnson
K K
KK
Wong
D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D000229:Dependovirus / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics; D015696:Gene Products, tat / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics*; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009355:Neomycin / Q000494:pharmacology; D016372:RNA, Antisense / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D014162:Transfection; D014779:Virus Replication / Q000235:genetics; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D016372:RNA, Antisense; D012333:RNA, Messenger; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus; D015500:Chloramphenicol O-Acetyltransferase; D009355:Neomycin