Category: RNAi Combination Therapy

Featured Paper:  "Lentiviral-mediated delivery of combined HIV-1 decoy TAR and Vif siRNA as a single RNA molecule that cleaves to inhibit HIV-1 in transduced cells."

Authors:  Barnor JS, Miyano-Kurosaki N, Yamaguchi K, Abumi Y, Ishikawa K, Yamamoto N.

Year of Publication: 2005

Journal:  Nucleosides Nucleotides Nucleic Acids. Vol. 24, 431-434

Online Availability:  Abstract from PubMed.

Significance

Several experiments have demonstrated the effectiveness of simultaneously using more than one potential RNA based therapy when fighting HIV.  In addition to RNAi, these experiments employ other RNA based methods such as decoy RNA, antisense RNA, and ribozymes (or catalytic RNA).  RNAi is most commonly combined with decoy RNA.

          Decoy RNA are sequences of RNA that are good at binding to certain proteins and inhibiting their function.  These RNA can be isolated by mixing the targeted protein with large numbers of small RNAs.  The RNAs that stick to the protein have the potential to become decoy RNAs, and could inhibit the work of the protein inside a cell.  For a definition of antisense and ribozyme therapy, please see the "Terms" section of this website.

          The featured paper, in addition to RNAi, uses decoy TAR RNA that binds to and inhibits the HIV-1 Tat protein.  The siRNA and the decoy RNA were encoded by the same construct and carried inside the same lentivirus.  The RNA encoded was cleaved inside the cell by DICER (referred to in the abstract as "the endogenous RNase III-like enzyme") to produce the separate siRNA and decoy RNA.  Both types of RNA produced a combined inhibition efficacy of over 80%.