Massachusetts Institute of Technology

Arbutus Biopharma Corporation

Joseph R Dorkin

Daniel Griffith Anderson

Robert Samuel Langer

Hao Yin

Owen Shea Fenton

Rebecca L McClellan

Arturo Jose Vegas

Tyler E Jacks

Kathryn Ann Whitehead

Kevin John Kauffman

Wen Xue

Yizhou Dong

Yunlong Zhang

Muthiah Manoharan

Kallanthottathil G Rajeev

Muthusamy Jayaraman

Akin Akinc

Delai Chen

Akinleye C Alabi

Jianxin Chen

Steven Ansell

Jayaprakash K Narayanannair

Xiaojun Qin

William Cantley

Robert S Langer

Ahmed A Eltoukhy

The present disclosure relates to compositions and methods for modifying a gene sequence, and for systems for delivering such compositions. For example, the disclosure relates to modifying a gene sequence using a CRISPR-Cas9 or other nucleic acid editing system, and methods and delivery systems for achieving such gene modification, such as viral or non-viral delivery systems.

Method for gene editing

Provided herein are compounds of Formula (I), and salts thereof, wherein each instance of Ris independently optionally substituted C-Calkenyl. Further provided are compositions comprising a compound of Formula (I) and an agent. Further provided are methods and kits using the compositions for delivering an agent to a subject or cell and for treating and/or preventing a range of diseases. Further provided are methods of preparing compounds of Formula (I) and precursors thereof. 

Alkenyl substituted 2,5-piperazinediones, compositions, and uses thereof

The present disclosure provides brush-poly(glycoamidoamine)-lipids (PGALs) (e.g., polymers of any one of Formulae (I)-(IV)) and methods of preparing the PGALs. A described PGAL may include poly(glycoamidoamine)-derived moieties (e.g., such as which may assist the PGAL and/or a complex of the PGAL and an agent to pass through cell membranes or be taken up by cells. Also provided are compositions including a described PGAL and an agent (e.g., polynucleotide, small molecule, peptide, or protein). The present disclosure also provides methods, kits, and uses that include or involve the PGALs or compositions for delivering an agent to a subject, tissue, or cell and/or for treating and/or preventing in a subject a range of diseases, such as genetic diseases, proliferative diseases, hematological diseases, neurological diseases, immunological diseases, gastrointestinal diseases, respiratory diseases, painful conditions, psychiatric disorders, musculoskeletal diseases, genitourinary diseases, and metabolic disorders 

Brush-poly (glycoamidoamine)-lipids and uses thereof

Delivery systems and kits for gene editing

&#x3b1;-Aminoamidine polymers and methods of preparing a-aminoamidine polymers by reacting by reacting one or more amines with one or more isocyanides and one or more aldehydes are described. Methods of preparing a-aminoamidine polymers from commercially available starting materials are also provided, wherein the starting materials are racemic or stereochemically pure. a-Aminoamidine polymers or salt forms thereof are preferably biodegradable and biocompatible and may be used in a variety of drug delivery systems and for other purposes as well such as, for example, coatings, additives, excipients, plastics, and materials, etc. Given the amino moiety of these &#x3b1;-aminoamidine polymers, they are particularly suited for the delivery of polynucleotides. Complexes, micelles, liposomes or particles containing the inventive &#x3b1;-aminoamidine polymers and polynucleotides can be prepared. The inventive &#x3b1;-aminoamidine polymers may also be used in preparing microparticles for drug delivery. They are particularly useful in delivering labile agents given their ability to buffer the pH of their surroundings.

Alpha-aminoamidine polymers and uses thereof

The present disclosure provides polyamine-fatty acid derived lipidoids (e.g., compounds of Formula (I) or (II)) and methods of preparing the lipidoids. A described lipidoid includes R&#x2014;C(&#x2550;O)&#x2014;O&#x2014; moieties (where R is a lipid moiety), which may be hydrolyzed into non-toxic fatty acids. Also provided are compositions including a described lipidoid and an agent (e.g., polynucleotide, small molecule, peptide, or protein). The present disclosure also provides methods, kits, and uses that involve the lipidoids or compositions for delivering an agent to a subject, tissue, or cell and/or for treating and/or preventing a range of diseases, such as genetic diseases, proliferative diseases, hematological diseases, neurological diseases, immunological diseases, gastrointestinal diseases, respiratory diseases, painful conditions, psychiatric disorders, and metabolic disorders. 

Polyamine-fatty acid derived lipidoids and uses thereof

Provided herein are lipidoids that may be prepared from the conjugate addition of alkylamines to acrylates. In some embodiments, provided lipidoids are biodegradable and may be used in a variety of drug delivery systems. Given the amino moiety of the lipidoids, they are well-suited for the delivery of polynucleotides, in addition to other agents. Nanoparticles containing the inventive lipidoids and polynucleotides have been prepared and have been shown to be effective in delivering siRNA.

Amine-containing lipidoids and uses thereof

The present invention provides novel 1,3,5-triazinane-2,4,6-trione derivatives, such as compounds of any one of Formulae (I) and (II), and salts thereof, and methods of preparing the compounds. Also provided are compositions including a compound of the invention and an agent (e.g., an siRNA, mRNA, or plasmid DNA). The present invention also provides methods and kits using the compositions for delivering an agent to a subject (e.g., to the liver, spleen, or lung of the subject) or cell and for treating and/or preventing a range of diseases, such as genetic diseases, proliferative diseases, hematological diseases, neurological diseases, liver diseases, and lung diseases. 

1,3,5-triazinane-2,4,6-trione derivatives and uses thereof

Growing community of inventors

Somerville, MA, United States of America

Joseph R Dorkin