Effective Inhibition of Human Immunodeficiency Virus 1 Replication by Engineered RNase P Ribozyme
Year: 2012
Type: article
Abstract: Using an in vitro selection procedure, we have previously isolated RNase P ribozyme variants that efficiently cleave an mRNA sequence in vitro. In this study, a variant was used to target the HIV RNA sequence in the tat region. The variant cleaved the tat RNA sequence in vitro about 20 times more efficiently than the wild type ribozyme. Our results provide the first direct evidence that combined mutations at nucleotide 83 and 340 of RNase P catalytic RNA from Escherichia coli (G(83) -> U(83) and G(340) -> A(340)) increase the overall efficiency of the ribozyme in cleaving an HIV RNA sequence. Moreover, the variant is more effective in reducing HIV-1 p24 expression and intracellular viral RNA level in cells than the wild type ribozyme. A reduction of about 90% in viral RNA level and a reduction of 150 fold in viral growth were observed in cells that expressed the variant, while a reduction of less than 10% was observed in cells that either did not express the ribozyme or produced a catalytically inactive ribozyme mutant. Thus, engineered ribozyme variants are effective in inhibiting HIV infection. These results also demonstrate the potential of engineering RNase P ribozymes for anti-HIV application.
Source: PLoS ONE
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Funders: National Natural Science Foundation of China, National Institutes of Health, National Key Research and Development Program of China, National Mega Project on Major Infectious Disease Prevention, National Institute of Allergy and Infectious Diseases, National Institute of Dental and Craniofacial Research
Awards: Bacteria Based Agents for Therapy of AIDS Associated Infections, G1828425977, Ribozymes for studies and treatment of cytomegalovirus infections, G2020058640, 人巨细胞病毒DNA引发酶UL70同宿主因子的相互作用研究, G2882242252, G2910884348, G302346924, 艾滋病毒与丙肝病毒共感染的分子机制研究, G3980981552, G400255378, G4162979394, G4640872055, G5203585564, G5298769716, G5693107550, G6602786995, 人巨细胞病毒复制必需蛋白与宿主细胞因子相互作用的生物学效应研究, G6779084299, G6990643879, G7026966229, G7431638370, G776984939, G779963157, G8182245486, G8594421566, G9000146525, G9000232082
OpenAlex ID: W2136107891