Small synthetic RNA, a method of preparing the same and uses...

Details Small synthetic RNA, a method of preparing the same and uses... Small synthetic RNA, a method of preparing the same and uses...

2005-03-10

2010-11-16

McGarry, Sean R (Department: 1635)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Carbohydrate doai

C536S023100, C536S024100, C536S024500, C435S006120, C435S375000, C435S455000, C435S320100, C435S091100, C435S091300, C435S091320

Reexamination Certificate

active

07833987

ABSTRACT:
Translation of the hepatitis C virus (HCV) RNA is mediated by the interaction of ribosomes and cellular proteins with an internal ribosome entry site (IRES) located within the 5′untranslated region (5′UTR). We have investigated whether small RNA molecules corresponding to the different stem-loop (SL) domains of the HCV IRES, when introduced in trans, can bind to the cellular proteins and antagonize their binding to the viral IRES, thereby inhibiting HCV IRES-mediated translation. We have found that an RNA molecule corresponding to SL III of the HCV IRES could efficiently inhibit HCV IRES-mediated translation in a dose-dependent manner without affecting cap-dependent translation. The SL III RNA was also found to bind efficiently to most of the cellular proteins which interacted with the HCV 5′UTR. A smaller RNA corresponding to SL e+f of domain III also strongly and selectively inhibited HCV IRES-mediated translation. This RNA molecule showed strong interaction with the ribosomal S5 protein and prevented the recruitment of the 40S ribosomal subunit by the HCV IRES. In conclusion our results demonstrate a novel approach to selectively block HCV RNA translation using a small RNA molecules mimicking the structure of the stem-loop IIIe+f subdomain of the HCV-IRES. The discovery provides a basis for developing a potent antiviral therapy targeting the interaction between the ribosome and the HCV-IRES RNA.

REFERENCES:
patent: 6127116 (2000-10-01), Rice et al.
patent: WO 94/05813 (1994-03-01), None
patent: WO 03/087138 (2003-10-01), None
Ray et al. NAR vol. 32(5):1678-87, Mar. 12, 2004.
Imbert, I., et al., “Hepatitis C virus IRES efficiency is unaffected by the genomic RNA 3'NTR even in the presence of viral structural or non-structural proteins”Journal of General Virology, 2003, vol. 84, pp. 1549-1557.
Tallet-Lopez, B., et al. “Antisense oligonucleotides targeted to the domain IIId of the hepatitis C virus IRES compete with 40S ribosomal subunit binding and prevent in vitro translation”Nucleic Acids Research, 2003, vol. 31, No. 2, pp. 734-742.

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