Carnegie Institution of Washington

University of Massachusetts

Leland Stanford Junior University

University of Texas System

Andrew Fire

Craig C Mello

Hiroaki Tabara

SiQun Xu

Samuel E Driver

Mary K Montgomery

Lisa Timmons

Stephen A Kostas

Alla Grishok

Scott D Boyd

Kyunga Seo

Jason Merker

Mark A Kay

Jiamiao Lu

Massa Shoura

Stephen Levene

Si-Qun Xu

Eleanor L Marshall

Weng-Onn Lui

Lia Gracey

Eleanor M Osborne

Lia E Gracey Maniar

Crag C Mello

Compositions and methods are provided for detection of dynamic loci in a genome, where such loci may comprise structural variations as a result of DNA recombination; DNA duplication, insertions, deletions, transpositions, and epigenetic changes. The methods may utilize microfluidic platforms and functionalized polymer matrices to allow determination of mechanisms of cell-type-specific, programmed genomic heterogeneity. The method and compositions allow determination of mechanisms of cell-type-specific, programmed genomic heterogeneity.

Detection and analysis of structural variations in genomes

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

The silencing effect of a spacer sequence, for example a bacterial backbone sequence in a plasmid or other episomal vector, on transgene expression is reversed by engineering of the spacer to include nucleosome exclusion sequences.

Nucleosome-excluding sequences (NES) as a DNA spacer in vectors results in prolonged transgene expression in eukaryotic cells

Methods are provided for the detection and analysis of clonality in a cell population, where parallel sequencing is applied to a nucleic acid sample obtained from the cell population, optionally a population of lymphocytes. Replicate samples are amplified, and sequenced, where identification of coincident sequences in two or more replicates is indicative of clonal expansion.

Measuring and monitoring of cell clonality

Measurement and monitoring of cell clonality

The invention encompasses methods for improving the level and/or sustainability of expression for a target nucleic acid in a eukaryotic cell comprising: (a) modifying the target nucleic acid to introduce or to comprise signals that limit or constrain the positions of nucleosome cores, and (b) introducing the modified target nucleic acid into the eukaryotic cell, wherein the modified target nucleic acid has improved levels and/or sustainability of expression compared to original unmodified nucleic acid.

Levels and/or sustainability of DNA-based gene expression

Genetic inhibition of double-stranded RNA

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

Baltimore, MD, United States of America

Andrew Fire