RNAi therapy for HIV infection: principles and practicalities.
Inside eukaryotic cells, small RNA duplexes, called small interfering RNAs (siRNAs), activate a conserved RNA interference (RNAi) pathway which leads to specific degradation of complementary target mRNAs through base-pairing recognition. As with other viruses, studies have shown that replication of the HIV-1 in cultured cells can be targeted and inhibited by synthetic siRNAs. The relative ease of siRNA design and the versatility of RNAi to target a broad spectrum of mRNAs have led to the promise that drug discovery in the RNAi pathway could be effective against pathogens. This review discusses the current experimental principles that guide the application of RNAi against HIV and describes challenges and limitations that need to be surmounted in order for siRNAs to become practical antiviral drugs. The practical use of RNAi therapy for HIV infection will depend on overcoming several challenges, including the ability to establish long-term expression of siRNA without off-target effects and the capacity to counteract mutant escape viruses.
Bennasser
Yamina
Y
Molecular Virology Section, Laboratory of Molecular Microbiology National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Yeung
Man Lung
ML
Jeang
Kuan-Teh
KT
D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D014779:Virus Replication / Q000187:drug effects
D034741:RNA, Small Interfering