Massachusetts Institute of Technology

Harvard College

Georgia Tech Research Corporation

The Broad Institute, Inc.

Mpeg La, L.l.c.

The Board Institute, Inc.

James E Dahlman

Feng Zhang

Daniel Griffith Anderson

Christopher G Levins

Avraham D Schroeder

Robert Samuel Langer

Hans-Peter Vornlocher

Philipp Hadwiger

Omar O Abudayyeh

Patrick D Hsu

David Arthur Scott

Jonathan Miles Brown

Kristin K H Neuman

Kalina Paunovska

Bernd Zetsche

Fei Ran

Robert S Langer, Jr

Cory Sago

Melissa Lokugamage

Robert Langer

The present invention provides inventive conjugated polyethyleneimine (PEI) polymers and conjugated aza-macrocycles (collectively referred to herein as “conjugated lipomers” or “lipomers”) containing one or more groups of the formula (iii): wherein Rand Rare as defined herein. Also provided are compositions comprising the inventive conjugated lipomers, and methods of preparation and use.

Conjugated lipomers and uses thereof

Disclosed herein are compositions and methods for identifying materials suitable for functional delivery of a bioactive agent to a target tissue. These compositions and methods have the advantage of simultaneously screening a library of materials for the ability to deliver a bioactive agent to a cell, tissue, or organ. The compositions and methods can also be used to confirm that the agent is delivered in a manner sufficient for function of the agent.

Multiplexed analysis of materials for tissue delivery

The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA or RNA-targeting systems comprising a novel DNA or RNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.

CRISPR enzymes and systems

Lipid nanoparticles and compositions thereof are disclosed herein. An exemplary nanoparticle composition includes an ionizable lipid, a phospholipid, a PEG-lipid, and a cholesterol modified with a hydroxyl group near the D-sterol ring. The disclosed nanoparticle compositions can target liver Kupffer cells and endothelial cells more preferentially than hepatocytes which should be beneficial in treating liver diseases in which dysfunctional Kupffer cells and endothelial cells are involved in disease pathogenesis.

Drug delivery systems containing oxidized cholesterols

Defined multi-conjugate oligonucleotides can have predetermined sizes and compositions. For example, in various embodiment, defined multi-conjugate oligonucleotides can have advantageous properties, for example in the form of defined multi-conjugate siRNA (i.e., including two, three or more siRNA) having enhanced intracellular delivery and/or multi-gene silencing effects. In various embodiment, the defined multi-conjugate oligonucleotides can be synthesized via new synthetic intermediates and methods. The defined multi-conjugate oligonucleotides can be used, for example, in reducing gene expression, biological research, treating or preventing medical conditions, or to produce new or altered phenotypes in cells or organisms.

Defined multi-conjugates oligonucleotides

The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems, wherein the guide sequence is modified by secondary structure to increase the specificity of the CRISPR-Cas system and whereby the secondary structure can protect against exonuclease activity and allow for 5' additions to the guide sequence.

Protected guide RNAS (pgRNAS)

Defined multi-conjugate oligonucleotides

The present invention generally relates to CRISPR systems or complexes, such as those with an escorted guide RNA.

Escorted and functionalized guides for CRISPR-Cas systems

The present invention provides inventive conjugated polyethyleneimine (PEI) polymers and conjugated aza-macrocycles (collectively referred to herein as 'conjugated lipomers' or 'lipomers') containing one or more groups of the formula (iii): wherein Rand Rare as defined herein. Also provided are compositions comprising the inventive conjugated lipomers, and methods of preparation and use.

Protected guide RNAS (PGRNAS)

Growing community of inventors

Cambridge, MA, United States of America

James E Dahlman