Development of RNase P ribozyme-based therapy against oral herpesvirus infections by HSV-1 and KSHV

Infections with human herpesviruses are known to be associated with oral lesions and other oral complications. For example, herpes simplex virus 1 (HSV-1) is the causative agent for cold sores. Kaposi's sarcoma-associated herpesvirus (KSHV) causes oral Kaposi's sarcoma (KS) and other oral complications among immunocompromised patients, such as HIV-positive individuals. Novel antiviral strategies are needed to effectively treat oral infections caused by HSV-1 and KSHV, given the limitations of current FDA-approved anti-HSV-1 and anti-KSHV therapies. Nucleic acid-based gene-interfering molecules, such as antisense oligonucleotides, ribozymes, and small interfering RNA (siRNA), are promising gene-targeting agents for therapeutic applications. Ribozymes derived from the catalytic RNA subunit of RNase P in Escherichia coli represent a novel class of RNA-based gene targeting molecules for degrading target mRNAs and modulating gene expression. Methods have been developed to engineer RNase P ribozymes that more effectively suppress gene expression. In this review, we summarize the recent advances in using RNase P ribozymes to block the expression of HSV-1 and KSHV genes and inhibit the infection of HSV-1 and KSHV. Moreover, we discuss the potential of engineered RNase P ribozymes as therapeutics to treat infections and associated diseases caused by HSV-1 and KSHV in the oral cavity.