Optimizing Electroporation Conditions for Intracellular Delivery of Morpholino Antisense Oligonucleotides Directed Against the Hepatitis C Virus Inter

Hepatitis C virus (HCV) contains a positive-sense, single-stranded RNA viral genome that encodes viral structural and nonstructural proteins (1 ). Initiation of translation is under control of the internal ribosome entry site (IRES) located within the viral 5′-nontranslated region (NTR) that is both highly conserved and structured (2 ). In contrast to cellular mRNAs that initiate translation at the extreme 5′ terminus, IRES elements direct the translational machinery directly to the initiator AUG codon. Mutations to various regions of the HCV IRES have proven deleterious to translation in numerous in vitro studies (reviewed in ref. 3 ). In addition, several antisense studies have demonstrated dramatic reduction in IRES activity (reviewed in ref. 3 ). Therefore, downregulation of IRES function has emerged as a valid therapeutic target for controlling HCV infection.