Characterization of the structure and variability of an internal region of hepatitis C virus RNA for M1 RNA guide sequence ribozyme targeting
Nadal, Anna (Hospital Universitari Vall d'Hebron)
Robertson, Hugh D. (Department of Biochemistry. Weill Medical College. Cornell University)
Guardia, Jaime (Hospital Universitari Vall d'Hebron)
Gómez, Jordi (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona. Departament de Medicina

Fecha:	2003
Resumen:	Accessibility to folded RNA and low potential of variation in the target RNA are crucial requirements for ribozyme therapy against virus infections. In hepatitis C virus (HCV), the sequence of the 5'UTR is conserved but the highly folded RNA structure severely limits the number of accessible sites. To expand investigation of targeting in the HCV genome, we have considered an internal genomic region whose sequence variation has been widely investigated and which has a particularly conserved RNA structure, which makes it accessible to the human RNase P in vitro. We have first mapped the accessibility of the genomic RNA to complementary DNAs within this internal genomic region. We performed a kinetic and thermodynamic study. Accordingly, we have designed and assayed four RNase P M1 RNA guide sequence ribozymes targeted to the selected sites. Considerations of RNA structural accessibility and sequence variation indicate that several target sites should be defined for simultaneous attack.
Ayudas:	Ministerio de Ciencia y Tecnología SAF1999-0108 Ministerio de Ciencia y Tecnología BIO00-0347 Ministerio de Sanidad y Consumo FISS-01/1351
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Lengua:	Anglès
Documento:	Article ; recerca ; Versió acceptada per publicar
Publicado en:	Journal of General Virology, Vol. 84 Núm. 6 (June 2003) , p. 1545-1548, ISSN 0022-1317

DOI: 10.1099/vir.0.18898-0

Postprint 12 p, 308.9 KB

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