Dose-response resistance to HIV-1/MuLV pseudotype virus ex vivo in a hairpin ribozyme transgenic mouse model.
We have investigated the efficacy of a hairpin ribozyme targeting the 5' leader sequence of HIV-1 RNA in a transgenic model system. Primary spleen cells derived from transgenic or control mice were infected with HIV-1/MuLV pseudotype virus. A significantly reduced susceptibility to infection in ribozyme-expressing transgenic spleen cells (P = 0.01) was shown. Variation of transgene-expression levels between littermates revealed a dose response between ribozyme expression and viral resistance, with an estimated cut off value below 0.2 copies of hairpin ribozyme per cell. These findings open up possibilities for studies on ribozyme efficacy and anti-HIV-1 gene therapy.
Andäng
M
M
Department of Medical Nutrition, Karolinska Institutet, 141 86 Huddinge, Sweden. michael.andang@cbt.ki.se
Hinkula
J
J
Hotchkiss
G
G
Larsson
S
S
Britton
S
S
Wong-Staal
F
F
Wahren
B
B
Ahrlund-Richter
L
L
D000818:Animals; D001483:Base Sequence; D003587:Cytomegalovirus / Q000235:genetics; D017931:DNA Primers; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial; D015497:HIV-1 / Q000187:drug effects*; D009052:Leukemia Virus, Murine / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016337:RNA, Catalytic / Q000235:genetics*
D017931:DNA Primers; D016376:Oligonucleotides, Antisense; D016337:RNA, Catalytic