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Several mono-, di-, tetra-, penta- and nonaribozymes were developed. These multitarget-ribozymes were targeted to cleave HIV-1 env RNA at up to nine different conserved sites. Each multitarget-ribozyme consisted of a chain of up to nine hammerhead motifs, each flanked by a different targeting sequence. The multitarget-ribozymes were functional in vitro and(More)
One of the hallmarks of progression of HIV-1/AIDS is the rapid depletion of CD4+T cells that is known to occur at the late stages of the disease when usually X4 tropic HIV-1 predominates. Besides direct killing of T lymphocytes, HIV-1 infection leads to extensive apoptosis of naïve/uninfected bystander T cells, which is predominantly mediated by HIV-1 TAT(More)
Two mono- and a di-RNA-cleaving DNA enzymes with the 10-23 catalytic motif were synthesized that were targeted to cleave at the conserved site/sites of the X gene of the hepatitis B virus. In each case, protein-independent but Mg(2+)-dependent cleavage of in vitro-synthesized full-length X RNA was obtained. Specific cleavage products were obtained with two(More)
It has become clear that mutations in a variety of host genes possess the ability to influence the progression of HIV-1, prominent among them are the chemokines. Stromal cell derived factor-1 (SDF-1), an alpha-chemokine, is a natural ligand for HIV-1 coreceptor-CXCR4 and a potent chemokine that blocks infection by X4 viruses. Nucleotide G to A transition(More)
The phenomenon of RNA interference mediated by small interfering RNAs (siRNAs) is a potent gene-silencing mechanism. A number of recent studies demonstrated inhibition of HIV-1 replication in cultured cells using this approach. To make further progress and harness this technology for HIV-1 gene therapy in a stem cell setting, in vivo studies using primary(More)
RNA interference (RNAi) is an important antiviral defense response in plants and invertebrates; however, evidences for its contribution to mammalian antiviral defense are few. In the present study, we demonstrate the anti-dengue virus role of RNAi in mammalian cells. Dengue virus infection of Huh 7 cells decreased the mRNA levels of host RNAi factors,(More)
Exploiting the phenomenon of RNA interference (RNAi), recent studies established the utility of monospecific small interfering RNAs (siRNAs) in suppressing HIV-1 infection. However, because of the high mutation rate of the HIV genome, there are considerable challenges in the design of fully efficacious gene therapeutic constructs. Therefore, approaches that(More)
BACKGROUND India has the third largest HIV-1 epidemic with 2.4 million infected individuals. Molecular epidemiological analysis has identified the predominance of HIV-1 subtype C (HIV-1C). However, the previous reports have been limited by sample size, and uneven geographical distribution. The introduction of HIV-1C in India remains uncertain due to this(More)
Selective inactivation of a target gene by antisense mechanisms is an important biological tool to delineate specific functions of the gene product. Approaches mediated by ribozymes and RNA-cleaving DNA enzymes (DNA enzymes) are more attractive because of their ability to catalytically cleave the target RNA. DNA enzymes have recently gained a lot of(More)
OBJECTIVE Ribozymes (Rzs) and DNA-enzymes (Dzs) possess the ability to prevent gene expression by cleaving target RNA in a catalytic and sequence-specific manner. Although Rzs or Dzs have been used earlier for HIV-1 gene suppression, the present study explored the possibility of using catalytic RNA and DNA simultaneously in a synergistic manner with the(More)