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RNA aptamers as emerging agents against hepatitis C virus replication

등록일
2007년 2월 21일 15시 09분 53초
접수번호
1246
발표코드
목14B2심 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
발표시간
목 14시 : 30분
발표형식
심포지엄
발표분야
생명화학 - Nucleic Acids and Nucleic Acid Binding Proteins
저자 및
공동저자
이성욱
단국대학교 분자생물학과,
Hepatitis C virus (HCV) is the main causative agent of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Although HCV affects more than 3% of the world population, specific and efficient anti-HCV therapy has not yet been developed. Here, we employed an RNA combinatorial library and isolated and characterized RNA aptamers for the HCV NS3 helicase domain and NS5B replicase essential for the HCV multiplication. These aptamers very avidly and specifically bound the target proteins, and moreover acted as potent decoys to competitively inhibit biochemical activity of each target protein. Of note, cytoplasmic expression of such aptamers efficiently impeded HCV subreplicon replication in human liver cells through interaction with target protein in the cells. Furthermore, we isolated high-affinity nuclease-resistant RNA aptamers with 2’-fluoro pyrimidines against the HCV NS5B. Direct introduction of these aptamers also showed efficient suppression of HCV replication in cells. These aptamers could be truncated up to chemically manufacturable 29 nt without compromising affinity and bioactivity. Therefore, identified aptamers could be applied to viral modulation through intracellular expression of the aptamer-encoding vector or direct delivery into cells of their chemically synthesized forms.

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