Targeting the HIV-1 RNA leader sequence with synthetic oligonucleotides and siRNA: chemistry and cell delivery.
New candidates for development as potential drugs or virucides against HIV-1 infection and AIDS continue to be needed. The HIV-1 RNA leader sequence has many essential functional sites for virus replication and regulation that includes several highly conserved sequences. The review describes the historical context of targeting the HIV-1 RNA leader sequence with antisense phosphorothioate oligonucleotides, such as GEM 91, and goes on to describe modern approaches to targeting this region with steric blocking oligonucleotide analogues having newer and more advantageous chemistries, as well as recent studies on siRNA, towards the attainment of antiviral activity. Recent attempts to obtain improved cell delivery are highlighted, including exciting new developments in the use of peptide conjugates of peptide nucleic acid (PNA) as potential virucides.
Turner
John J
JJ
Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK.
Fabani
Martin
M
Arzumanov
Andrey A
AA
Ivanova
Gabriela
G
Gait
Michael J
MJ
D020121:5' Untranslated Regions / Q000187:drug effects / Q000235:genetics; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000737:chemistry; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage* / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry; D012367:RNA, Viral / Q000187:drug effects / Q000235:genetics; D013873:Thionucleotides / Q000008:administration & dosage / Q000737:chemistry
D020121:5' Untranslated Regions; D019380:Anti-HIV Agents; D020319:Oligodeoxyribonucleotides, Antisense; D034741:RNA, Small Interfering; D012367:RNA, Viral; D013873:Thionucleotides; C079996:GEM91