Nucleic Acids Research, Vol 26, Issue 22 5093-5101, Copyright © 1998 by Oxford University Press
ML Pierce and DE Ruffner
Antisense-mediated gene inhibition uses short complementary DNA or RNA
oligonucleotides to block expression of any mRNA of interest. A key
parameter in the success or failure of an antisense therapy is the
identification of a suitable target site on the chosen mRNA. Ultimately,
the accessibility of the target to the antisense agent determines target
suitability. Since accessibility is a function of many complex factors, it
is currently beyond our ability to predict. Consequently, identification of
the most effective target(s) requires examination of every site. Towards
this goal, we describe a method to construct directed ribozyme libraries
against any chosen mRNA. The library contains nearly equal amounts of
ribozymes targeting every site on the chosen transcript and the library
only contains ribozymes capable of binding to that transcript. Expression
of the ribozyme library in cultured cells should allow identification of
optimal target sites under natural conditions, subject to the complexities
of a fully functional cell. Optimal target sites identified in this manner
should be the most effective sites for therapeutic intervention.
ARTICLES
Construction of a directed hammerhead ribozyme library: towards the identification of optimal target sites for antisense-mediated gene inhibition
Department of Pharmaceutics and Pharmaceutical Chemistry and Department of Bioengineering, University of Utah, 421 Wakara Way, Suite 318, Salt Lake City, UT 84108, USA.
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