Articles by Autumn J. Ruiz in JoVE
MicroRNA-based Regulation of Picornavirus Tropism Autumn J. Ruiz1, Stephen J. Russell1 1Department of Molecular Medicine, Mayo Clinic College of Medicine We describe here a method for regulating picornavirus tropism by incorporating sequences complementary to specific microRNAs into the viral genome. This protocol can be adapted to all different classes of viruses with modifications based upon the length and nature of their life cycle.
Other articles by Autumn J. Ruiz on PubMed
MicroRNAs and Oncolytic Viruses Current Opinion in Virology. Aug, 2015 | Pubmed ID: 25863717 MicroRNAs regulate gene expression in mammalian cells and often exhibit tissue-specific expression patterns. Incorporation of microRNA target sequences can be used to control exogenous gene expression and viral tropism in specific tissues to enhance the therapeutic indices of oncolytic viruses expressing therapeutic transgenes. Continued development of this targeting strategy has resulted in the generation of unattenuated oncolytic viruses with enhanced potency, broad species-tropisms and reduced off-target toxicities in multiple-tissues simultaneously. Furthermore, oncolytic viruses have been used to enhance the delivery, duration and therapeutic efficacy of microRNA-based therapeutics designed to either restore or inhibit the function of dysregulated microRNAs in cancer cells. Recent efforts focused on combining oncolytic virotherapy and microRNA regulation have generated increasingly potent and safe cancer therapeutics.
MicroRNA-Detargeted Mengovirus for Oncolytic Virotherapy Journal of Virology. Apr, 2016 | Pubmed ID: 26865716 Mengovirus, a member of thePicornaviridaefamily, has a broad cell tropism and can cause encephalitis and myocarditis in multiple mammalian species. Attenuation has been achieved by shortening the polycytidine tract in the 5' noncoding region (NCR). A poly(C)-truncated strain of mengovirus, vMC24, resulted in significant tumor regression in immunocompetent BALB/c mice bearing syngeneic MPC-11 plasmacytomas, but the associated toxicities were unacceptable. To enhance its safety profile, microRNA target sequences complementary to miR-124 or miR-125 (enriched in nervous tissue), miR-133 and miR-208 (enriched in cardiac tissue), or miR-142 (control; enriched in hematopoietic tissues) were inserted into the vMC24NCRs. The microRNA-detargeted viruses showed reduced replication and cell killing specifically in cells expressing the cognate microRNAs, but certain insertions additionally were associated with nonspecific suppression of viral fitnessin vivo. In vivotoxicity testing confirmed that miR-124 targets within the 5' NCR suppressed virus replication in the central nervous system while miR-133 and miR-208 targets in the 3' NCR suppressed viral replication in cardiac tissue. A dual-detargeted virus named vMC24-NC, with miR-124 targets in the 5' NCR and miR-133 plus miR-208 targets in the 3' NCR, showed the suppression of replication in both nervous and cardiac tissues but retained full oncolytic potency when administered by intratumoral (10(6)50% tissue culture infectious doses [TCID50]) or intravenous (10(7)to 10(8)TCID50) injection into BALB/c mice bearing MPC-11 plasmacytomas. Overall survival of vMC24-NC-treated tumor-bearing mice was significantly improved compared to that of nontreated mice. MicroRNA-detargeted mengoviruses offer a promising oncolytic virotherapy platform that merits further development for clinical translation.