Novel approach to gene regulation can activate multiple genes simultaneously

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Posted August 28, 2013

By creating a powerful new gene regulation system called CRISPR-on, Whitehead Institute researchers now have the ability to increase the expression of multiple genes simultaneously and precisely manipulate each gene’s expression level. The system is effective in both mouse and human cells as well as in mouse embryos.

“CRISPR-on is a tool that will be very useful for studying many biological processes, particularly for studying gene functions and gene networks,” says Whitehead Founding Member Rudolf Jaenisch. “In contrast to RNA interference, which is commonly used to inactivate gene activity, the CRISPR-on system allows activation of cellular genes. The technology substantially expands our ability to change gene expression in cultured cells and animals..”

The system, called CRISPR-on, is a modified version of CRISPR/Cas (for “clustered regularly interspaced short palindromic repeat/CRISPR associated”), which taps into a bacterial defense system against viral intruders. CRISPR/Cas relies on an enzyme, Cas9, which cuts DNA at locations specified by single guide RNAs (sgRNAs). For CRISPR-on, the Whitehead team modified the Cas9 enzyme by eliminating its ability to cleave DNA and adding a transcription activation domain. The resulting enzyme can increase gene expression without permanently changing the DNA.

The new system is described this week in the journal Cell Research.

CRISPR-on’s ability to activate only the desired genes at varying levels could be used to help scientists improve our understanding of transcription network underlying a variety of diseases and potentially find new ways to treat them.


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