| Abstrakt: |
Simple Summary: Acquired immunodeficiency syndrome (AIDS), which is caused by human immunodeficiency virus (HIV), is a significant global public health concern. It is critical to generate new compounds and explore novel strategies against HIV infection to eliminate HIV-associated diseases such as AIDS. RNA enzymes, or ribozymes, represent a novel class of gene-targeting molecules with promising therapeutic potentials for the treatment of human diseases. In this report, we showed that an engineered ribozyme, called RNase P ribozyme, was able to shut down the expression of a cellular co-receptor for HIV and suppress HIV infection in human cells. Furthermore, our results suggest that the constructed anti-HIV ribozyme is highly specific, only inhibiting the expression of its target HIV co-receptor but not other co-receptors for HIV. These results demonstrate the utility of RNase P ribozyme as a gene-targeting agent for anti-HIV therapy and, furthermore, facilitate the development of new drugs and novel approaches for the treatment and prevention of HIV infection and AIDS. Developing novel antiviral agents and approaches is essential for the treatment against human and zoonotic viruses. We had previously produced RNase P-based ribozyme variants capable of efficiently cleaving mRNA in vitro. Here, engineered ribozymes were constructed from an RNase P ribozyme variant to target the mRNA encoding human CC-chemokine receptor 5 (CCR5), an HIV co-receptor. The constructed ribozyme efficiently cleaved the CCR5 mRNA in vitro. In cells expressing the engineered ribozyme, CCR5 expression diminished by more than 90% and the infection of HIV (R5 strain Ba-L) decreased by 200-fold. The ribozyme-expressing cells resistant to R5 strain Ba-L still supported the infection of HIV X4 strain IIIB due to its use of CXCR4 instead of CCR5 as the co-receptor. Thus, the ribozyme is specific against CCR5 but not CXCR4. This indicates that RNase P ribozyme is effective and specific against CCR5 to diminish HIV infection, and also displays the viability of developing engineered RNase P ribozymes against human and zoonotic viruses. [ABSTRACT FROM AUTHOR] |
