Design and Evaluation of Clinically Relevant SOFA-HDV Ribozymes Targeting HIV RNA
Nucleic acid therapies targeting HIV replication have the potential to be used in conjunction with or in place of the standard small-molecule therapies. Among the different classes of nucleic acid therapies, several ribozymes (Rzs, RNA enzymes) have been developed to target HIV RNA. The design of Rzs targeting HIV RNA is complicated by the sequence diversity of viral strains and the structural diversity of their target sites. Using the SOFA-HDV Rz as an example, this chapter describes methods that can be used to design Rzs for controlling HIV replication. We describe how to (1) identify highly conserved Rz target sites in HIV RNA; (2) generate a set of Rzs with the potential to be used as therapeutics; and (3) screen these Rzs for activity against HIV production.
Key wordsHIV Ribozymes Sequence conservation Antisense RNA therapeutics
- 8.Lainé S, Scarborough RJ, Lévesque D, Didierlaurent L, Soye KJ, Mougel M, Perreault JP, Gatignol A (2011) In vitro and in vivo cleavage of HIV-1 RNA by new SOFA-HDV ribozymes and their potential to inhibit viral replication. RNA Biol 8(2):343–353Google Scholar
- 21.Lee SK, Dykxhoorn DM, Kumar P, Ranjbar S, Song E, Maliszewski LE, François-Bongarçon V, Goldfeld A, Swamy NM, Lieberman J, Shankar P (2005) Lentiviral delivery of short hairpin RNAs protects CD4 T cells from multiple clades and primary isolates of HIV. Blood 106(3):818–826PubMedCentralPubMedCrossRefGoogle Scholar
- 28.Peden KWC, Martin MA (1995) Virological and molecular genetic techniques for studies of established HIV isolates. In: Karn J (ed) HIV, a practical approach: virology and immunology. IRL Press, Oxford, pp 21–45Google Scholar
- 33.Butler PJG (1995) Biological safety when working with HIV. In: Karn J (ed) HIV, a practical approach: virology and immunology. IRL Press, Oxford, pp 1–12Google Scholar