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Optimizing the design of oligonucleotides for homology directed gene targeting.


ABSTRACT:

Background

Gene targeting depends on the ability of cells to use homologous recombination to integrate exogenous DNA into their own genome. A robust mechanistic model of homologous recombination is necessary to fully exploit gene targeting for therapeutic benefit.

Methodology/principal findings

In this work, our recently developed numerical simulation model for homology search is employed to develop rules for the design of oligonucleotides used in gene targeting. A Metropolis Monte-Carlo algorithm is used to predict the pairing dynamics of an oligonucleotide with the target double-stranded DNA. The model calculates the base-alignment between a long, target double-stranded DNA and a probe nucleoprotein filament comprised of homologous recombination proteins (Rad51 or RecA) po

SUBMITTER: Mine-Hattab J 

PROVIDER: S-EPMC3071677 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature