Compositions, methods and use of synthetic lethal screening
AssigneesThe Board Institute, Inc., Massachusetts Institute of Technology
InventorMyriam Heiman
Life of this patent
Estimating the term…
Abstract
The present invention generally relates to methods of identifying modulators of central nervous system diseases and the use of the modulators in treatment and diagnosis. The methods utilize a novel high throughput screen that includes injection of a library of barcoded viral vectors expressing shRNA's, CRISPR/Cas systems or cDNA's into animal models of disease and detecting synthetic lethality.
Claims20
A method of screening for modulators of a disease comprising:
- (a) administering to each of a first and second mammal of the same species at least one vector, each vector comprising a regulatory element operably linked to a nucleotide sequence that is transcribed in vivo,
- wherein the first mammal is a model of a human disease and the second mammal is a normal control mammal not a model of a human disease, and
- wherein the nucleotide sequence encodes a protein coding gene, or a short hairpin RNA, or a CRISPR/Cas system;
- (b) harvesting DNA from the first mammal and the second mammal;
- (c) identifying the vectors by sequencing the harvested DNA;
- and
- (d) comparing the representation of each vector from the first mammal and the second mammal, whereby a differential representation in the first mammal indicates that the protein coding gene, or short hairpin RNA target, or CRISPR/Cas system target is a modulator of the disease.
A method of treating a nervous system disease comprising activating expression of Gpx6 in the central nervous system of a subject in need thereof suffering from the disease.
A method of treating a nervous system disease comprising expressing Gpx6 in the central nervous system of a subject in need thereof suffering from the disease.
A method of treating a nervous system disease comprising introducing into a subject in need thereof suffering from the disease a CRISPR-Cas9 based system configured to target Gpx6.
A method of determining a prognosis for a central nervous system disease comprising:
- (e) obtaining a RNA sample from a patient suffering from a central nervous system disease;
- (f) assaying the level of Gpx6 gene expression;
- and
- (g) comparing the levels of Gpx6 gene expression to a control level determined by testing healthy subjects, wherein the prognosis is worse if Gpx6 gene expression is lower than the control level.
An antibody comprising a heavy chain and a light chain, wherein the antibody binds to an antigenic region of the Gpx6 protein comprising SEQ ID No:
- 1.
Dependencies are inferred from the claim text.