University of Massachusetts

Carnegie Institution of Washington

Craig C Mello

Andrew Fire

Hiroaki Tabara

Alla Grishok

Phillip D Zamore

SiQun Xu

Samuel E Driver

Mary K Montgomery

Lisa Timmons

Juanita McLachlan

Stephen A Kostas

Gyorgy Hutvagner

Krishna Sumanth Ghanta

Jonathan Watts

Erik J Sontheimer

Gyoergy Hutvagner

Aamir Mir

Gregoriy Dokshin

Hassan Gneid

Juanita Mclachlan

Philip D Zamore

Gyorgy Hutvanger

The disclosure provides novel methods and compositions for gene editing. In particular, the disclosure relates to compositions and methods of making modified nucleic acid donor templates for highly efficient and precise gene editing.

Compositions and methods for improved gene editing

The disclosure provides novel methods and compositions for gene editing. In particular, the disclosure relates to compositions and methods of making nucleic acid donor templates for highly efficient and precise gene editing.

The invention provides engineered RNA precursors that when expressed in a cell are processed by the cell to produce targeted small interfering RNAs (siRNAs) that selectively silence targeted genes (by cleaving specific mRNAs) using the cell's own RNA interference (RNAi) pathway. By introducing nucleic acid molecules that encode these engineered RNA precursors into cells in vivo with appropriate regulatory sequences, expression of the engineered RNA precursors can be selectively controlled both temporally and spatially, i.e., at particular times and/or in particular tissues, organs, or cells.

In vivo production of small interfering RNAs that mediate gene silencing

A process is provided of introducing an RNA into a living cell to inhibit gene expression of a target gene in that cell. The process may be practiced ex vivo or in vivo. The RNA has a region with double-stranded structure. Inhibition is sequence-specific in that the nucleotide sequences of the duplex region of the RNA and of a portion of the target gene are identical. The present invention is distinguished from prior art interference in gene expression by antisense or triple-strand methods.

Genetic inhibition by double-stranded RNA

In vivo production of small interfering RNAS that mediate gene silencing

Vivo production of small interfering RNAs that mediate gene silencing

Genetic inhibition of double-stranded RNA

The invention provides engineered RNA precursors that when expressed in a cell are processed by the cell to produce targeted small interfering RNAs (siRNAs) that selectively silence targeted genes (by cleaving specific mRNAs) using the cell's own RNA interference (RNAi) pathway. By introducing nucleic acid molecules that encode these engineered RNA precursors into cells in vitro with appropriate regulatory sequences, expression of the engineered RNA precursors can be selectively controlled both temporally and spatially, i.e., at particular times and/or in particular tissues, organs, or cells.

Genes involved in double-stranded RNA interference (RNAi pathway genes) are identified and used to investigate the RNAi pathway. The genes and their products are also useful for modulating RNAi pathway activity.

RNA interference pathway genes as tools for targeted genetic interference

Growing community of inventors

Shrewsbury, MA, United States of America

Craig C Mello