Exact Sciences Corporation

Exact Laboratories, Inc.

Genzyme Corporation

Genetics Research, LLC

Esoterix Genetic Laboratories, LLC

Other

Predictive Biosciences Corporation

Hologic, Inc.

Physicians Choice Laboratory Services, LLC

Mayo Foundation for Medical Education and Research

Ig Laboratories, Inc.

Mayo Clinic

Anthony P Shuber

Stanley N Lapidus

William Glover

William Pierceall

Howard B Kaufman

Erin Coffman

Duncan H Whitney

Steven Hecht

Paul MacLean

Thomas C Meyers

Eugene Chiu

Kevin M Ulmer

Gail E Radcliffe

Lisa Kann

David Alan Ahlquist

George Q Daley

Steven J Laken

Frederick A Huntress, Jr

Patrick R Waller

David A Alquist

James K Moore

Paul Maclean

The present disclosure describes a method of treating a sample comprising cells with a process of partial lysing. Cells are exposed to a process such as bead beating that lyses some cells in the mixture. The process generates a resultant sample mixture that is suitable for both cell morphology screening and genetic screening.

Method of partial lysis and assay

Provided herein are methods of detecting nucleic acids. The nucleic acid of interest may be detected by using Cas endonuclease to degrade substantially all nucleic acid in a sample except for the nucleic acid of interest, leaving the nucleic acid of interest isolated and amenable to detection. In related methods, Cas endonuclease complexes are used to protect the nucleic acid of interest while unprotected nucleic acid is digested, e.g., by exonuclease, after which the isolated nucleic acid of interest is detected.

Detection of targeted sequence regions

The invention provided methods and devices for performing sequential, regulated multiplex reactions in a single tube without the addition or removal of contents from the tube.

Regulated multiplex reactions in a single tube

The invention provides methods for determining the mutation burden of a tumor by assaying tumor DNA that is representative of genetic loci that are themselves representative of genetics of the tumor. The assayed tumor DNA may be itself agnostic as to loci, so long as it is representative of loci that are representative of tumor mutation burden. The invention provides for assays in which the tumor DNA being sequenced or tested can be something other than, and possibly less than, a full panel of oncogenes that is expected to stand for a tumor's mutational load.

Tumor mutation burden

The present disclosure describes a method of treating a sample comprising cells with a process of partial lysing. Cells are exposed to a process such as bead beating that lyses some cells in the mixture. The process generates a resultant sample mixture that is suitable for both cell morphology screening and genetic screening. A first portion of the partially lysed sample can be mounted on a slide and observed for atypical cells and cytologic abnormalities. A second portion of the partially lysed sample can be screened for genetic markers known to correlate with a risk of cervical cancer. The method is particularly useful for cervical screening, where a combination of cytology and genetic screening present a more complete picture of cervical health. The disclosed method streamlines the diagnostic process for protocols that require both types of assays, without compromising screening accuracy.

The invention provides methods for detecting small mutations and structural alterations in DNA by using binding proteins to protect those features while digesting unprotected DNA in a sample. To detect small mutations, a protein that binds exclusively to the mutation of interest, and not to wild-type, is used. For structural alterations, binding proteins are used that flank a breakpoint of the alteration. After digestion of unbound, unprotected nucleic acid in the sample, the mutation- or breakpoint-containing segment remains as an isolated DNA fragment. The sample is then assayed to detect any fragment of DNA and the detection of the fragment indicates the presence of the mutation or breakpoint in the subject.

Methods for rare event detection

Methods for capturing and characterizing low frequency nucleic acid molecules indicative of diseases such as cancer (e.g. adenomas or early stage cancers) are provided. In some aspects, a low complexity capture technique is combined with a high complexity analytical technique. In some aspects, samples may be analyzed using a digital analysis and/or a single molecule sequencing technique.

Analysis of heterogeneous nucleic acid samples

The invention provides methods for detecting and monitoring diseases associated with genetic abnormalities in a subject.

Method for monitoring disease progression or recurrence

The invention generally relates to methods for detecting a target nucleic acid and a target protein in a single assay.

Detection of nucleic acids and proteins

This invention generally relates to compositions and methods for targeted delivery of chemotherapeutic agents to cancerous and pre-cancerous cells, thereby treating a cancer in a subject.

Compositions and methods for treating cancer

Growing community of inventors

Mendon, MA, United States of America

Anthony P Shuber