Prof. Jyoti Chattopadhyaya from Uppsala University and colleagues from India have synthesised modified siRNAs targetting the TAR region of HIV-1, some of which exhibit a four-fold enhanced half-life in serum over the native unmodified siRNA. The best compound synthesised had an IC50 more than three-fold lower than that of the native and two-fold lower than that of the existing locked nucleic acid (LNA) modified counterpart. The strategy to chemically modify the native siRNAs by substitution with the jcLNA can be considered as a significant development, leading to both enhanced siRNA efficiency and serum stability over that of the native. Read more in MedChemComm.
Friday Lecture Series
“Dicer and Beyond: Regulatory RNA Processing and Function”
Jennifer A. Doudna, Ph.D., professor, departments of molecular and cell biology and of chemistry; investigator, Howard Hughes Medical Institute
University of California, Berkeley
May 8, 2009
3:45 p.m.-5:00 p.m. (Refreshments, 3:15 p.m., Abby Lounge)
Aggarwal, A. K., and J. A. Doudna. 2005. Protein-nucleic acid interactions: Unlocking mysteries old and new. Current opinion in structural biology. 15(1 SPEC. ISS.):65-67.
Fukunaga, R., and J. A. Doudna. 2009. dsRNA with 5′ overhangs contributes to endogenous and antiviral RNA silencing pathways in plants. EMBO Journal. 28(5):545-555.
Jinek, M., and J. A. Doudna. 2009. A three-dimensional view of the molecular machinery of RNA interference. Nature. 457(7228):405-412.
Ma, E., I. J. MacRae, J. F. Kirsch, and J. A. Doudna. 2008. Autoinhibition of human dicer by its internal helicase domain. Journal of Molecular Biology. 380(1):237-243.
MacRae, I. J., and J. A. Doudna. 2007. Ribonuclease revisited: Structural insights into ribonuclease III family enzymes. Current opinion in structural biology. 17(1):138-145.
MacRae, I. J., K. Zhou, and J. A. Doudna. 2007. Structural determinants of RNA recognition and cleavage by dicer. Nature Structural and Molecular Biology. 14(10):934-940.
MacRae, I. J., K. Zhou, F. Li, A. Repic, A. N. Brooks, W. Z. Cande, P. D. Adams, and J. A. Doudna. 2006. Structural basis for double-stranded RNA processing by dicer. Science. 311(5758):195-198.