Massachusetts Institute of Technology

Children's Medical Center Corporation

Living Proof, Inc.

Translate Bio, Inc.

Other

Whitehead Institute for Biomedical Research

USA As Represented by Secretary of the Navy

The General Hospital Corporation

The Brigham and Women's Hospital, Inc.

Politecnico Di Milano

The University of Nottingham

Seattle Children's Hospital

Shire Human Genetic Therapies, Inc.

Performance Indicator, LLC

The Broad Institute, Inc.

Daniel Griffith Anderson

Robert Samuel Langer

Arturo Jose Vegas

Minglin Ma

Omid Veiseh

Joshua C Doloff

David Thomas Puerta

Ronald P McLaughlin

Yizhou Dong

Joseph R Dorkin

Kevin Thomas Love

Delai Chen

Christopher G Levins

David M Lynn

Susan Alice Williams

Bryan Scott Akcasu

Amir Nashat

Mitchell John DeRosa

Kathryn Ann Whitehead

Richard Matthew Ramirez

Robert Alexander Wesselhoeft

Yunlong Zhang

Michael W Heartlein

Feng Zhang

Akinleye C Alabi

Hao Yin

Kevin John Kauffman

Kerry Peter Mahon

Frank DeRosa

David Putnam

Mansoor M Amiji

Tyler E Jacks

Christian J Kastrup

Avraham D Schroeder

Piotr S Kowalski

Kaitlin M Bratlie

Yi Heng Chen

James E Dahlman

Owen Shea Fenton

James C Kaczmarek

Susan Alice Thiell

Jeffrey Michael Karp

Rohit Nandkumar Karnik

Seungpyo Hong

Andreas Zumbuehl

Suman Bose

Wen Xue

Asha Kumari Patel

Tram T Dang

Akin Akinc

Hidde L Ploegh

Eric Andrew Appel

Omar Khan

Charles Daniel Anderson

Allen T Horhota

Brian Goodman

Rosemary Lynn Kanasty

Gregory T Zugates

Lei Miao

Yuxuan Huang

Shinichiro Fuse

Raffaella Squilloni

Jasdave S Chahal

Omid C Farokhzad

Carlo Giovanni Traverso

Edward D Kingsley

Steven R Little

Samuel R Browd

Jason Alan Burdick

Robert Todd Winskowicz

Paul Williams

Davide Moscatelli

Daniel Blankschtein

Randall Jeffrey Platt

Frank Derosa

Rebecca L McClellan

Ying Mei

Virginia Spanoudaki

Matthew J Webber

David A Canner

Zhen Gu

Grady Roe

Linxian Li

Benjamin C Tang

Robert S Langer, Jr

Alan Pradip Jasanoff

Robert S Langer

Martyn Christopher Davies

Wendy Liu

Carl Magnus Schoellhammer

Weiheng Wang

Baris Erinc Polat

Aviad Hai

Robert Langer

Mingming Ma

Alex Aimetti

William Shain

Morgan Russell Alexander

Brian W Hanak

Hung-Chieh Chou

Compositions and methods for modified dendrimer nanoparticle ('MDNP') delivery of therapeutic, prophylactic and/or diagnostic agent such as large repRNA molecules to the cells of a subject have been developed. MDNPs efficiently drive proliferation of antigen-specific T cells against intracellular antigen, and potentiate antigen-specific antibody responses. MDNPs can be multiplexed to deliver two or more different repRNAs to modify expression kinetics of encoded antigens and to simultaneous deliver repRNAs and mRNAs including the same UTR elements that promote expression of encoded antigens.

Compositions and methods for modified dendrimer nanoparticle delivery

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

Products, such as devices, prostheses, and materials, whose surfaces have been modified in order to impart beneficial properties to these products are disclosed. The surface-modified products have improved biocompatibility compared to a corresponding product that lacks the modification. Following implantation in a subject, the surface-modified products induce a lower foreign-body response, compared to a corresponding unmodified product.

Materials with improved biocompatibility

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 lipidoid compounds of Formulae (I) and (II), and pharmaceutically acceptable salts, co-crystals, tautomers, stereoisomers, solvates, hydrates, polymorphs, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive lipidoid compounds, compositions, or formulations for treating and/or preventing diseases (e.g., genetic disease, proliferative disease, hematological disease, neurological disease, painful condition, psychiatric disorder, metabolic disorder, long-term medical condition, inflammatory disease, autoinflammatory disease, liver disease, lung disease, spleen disease, familial amyloid neuropathy, cardiovascular disease, viral infection, infectious disease, fibrotic condition, or autoimmune disease) in a subject, methods for synthesizing the compounds described herein, and compounds described herein synthesized by the synthetic methods described herein. The compounds are effective carriers for the delivery of an agent such as a polynucleotide (e.g., RNA) to a cell.

Ionizable lipidoids and their uses

Covalently modified alginate polymers, possessing enhanced biocompatibility and tailored physiochemical properties, as well as methods of making and use thereof, are disclosed herein. The covalently modified alginates are useful as a matrix for coating of any material where reduced fibrosis is desired, such as encapsulated cells for transplantation and medical devices implanted or used in the body.

Modified alginates for anti-fibrotic materials and applications

Disclosed are methods and constructs for engineering circular RNA Disclosed is a vector for making circular RNA, said vector comprising the following elements operably connected to each other and arranged in the following sequence: a) a 5′ homology arm, b) a 3′ group I intron fragment containing a 3′ splice site dinucleotide, c) an optional 5′ spacer sequence, d) a protein coding or noncoding region, e) an optional 3′ spacer sequence, f) a 5′ Group I intron fragment containing a 5′ splice site dinucleotide, and g) a 3′ homology arm. This vector allows production of a circular RNA that is translatable or biologically active inside eukaryotic cells. In one embodiment, the vector can comprise the 5′ spacer sequence, but not the 3′ spacer sequence. In yet another embodiment, the vector can also comprise the 3′ spacer sequence, but not the 5′ spacer sequence.

Circular RNA for translation in eukaryotic cells

The present invention provides, among other things, methods of delivering mRNA in vivo, including administering to a subject in need of delivery a composition comprising an mRNA encoding a protein, encapsulated within a liposome such that the administering of the composition results in the expression of the protein encoded by the mRNA in vivo, wherein the liposome comprises a cationic lipid of formula I-c: or a pharmaceutically acceptable salt thereof.

Lipid formulations for delivery of messenger RNA

Methods and constructs for engineering circular RNA are disclosed. In some embodiments, the methods and constructs comprise a vector for making circular RNA, the vector comprising the following elements operably connected to each other and arranged in the following sequence: a.) a 5′ homology arm, b.) a 3′ group I intron fragment containing a 3′ splice site dinucleotide, c.) optionally, a 5′ spacer sequence, d.) a protein coding or noncoding region, e.) optionally, a 3′ spacer sequence, f) a 5′ Group I intron fragment containing a 5′ splice site dinucleotide, and g.) a 3′ homology arm, the vector allowing production of a circular RNA that is translatable or biologically active inside eukaryotic cells. Methods for purifying the circular RNA produced by the vector and the use of nucleoside modifications in circular RNA produced by the vector are also disclosed.

The disclosure relates to compositions comprising and methods for chemical modification of single guide RNA (sgRNA), tracrRNA and/or crRNA used individually or in combination with one another or Cas system components. Compositions comprising modified ribonucleic acids have been designed with chemical modification for even higher efficiency as unmodified native strand of sgRNA. Administration of modified ribonucleic acids will allow decreased immune response when administered to a subject, increased stability, increased editing efficiency and facilitated in vivo delivery of sgRNA via various delivery platforms. The disclosure also relates to methods of decreasing off-target effect of CRISPR and a CRISPR complex.

Structure-guided chemical modification of guide RNA and its applications

Circular RNA and transfer vehicles, along with related compositions and methods are described herein. In some embodiments, the inventive circular RNA comprises group I intron fragments, spacers, an IRES, duplex forming regions, and an expression sequence. In some embodiments, the expression sequence encodes a chimeric antigen receptor (CAR). In some embodiments, circular RNA of the invention has improved expression, functional stability, immunogenicity, ease of manufacturing, and/or half-life when compared to linear RNA. In some embodiments, inventive methods and constructs result in improved circularization efficiency, splicing efficiency, and/or purity when compared to existing RNA circularization approaches.

Circular RNA compositions and methods

A cross-modal interface includes a multi-modal sensor configured to concurrently receive multiple input signals with each input signal being provided from a different imaging modality and in response thereto providing a single cross-modal output signal to processing circuitry which processes the single cross-modal output signal provided thereto and generates an output comprising information obtained or otherwise derived from each of or a combination of the different imaging modalities.

Interface responsive to two or more sensor modalities

Provided herein are branched poly(beta-amino esters) (PBAE) useful as vehicles for the delivery of therapeutic agents, such as nucleic acids. The disclosed polymers form stable compositions, and are suitable for the delivery of therapeutic agents via nebulization. Compositions of the disclosed polymers are capable of delivering therapeutic agents such as mRNA to lung epithelial cells.

Poly(beta-amino esters) and uses thereof

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 relates to improvements in the selection and formulation of PBAE polymers using a design of experiment approach, in which statistical methods are used to limit possible experimental conditions. The present disclosure relates to improved PBAE polymers and formulations.

Polymer-lipids and compositions

Growing community of inventors

Framingham, MA, United States of America

Daniel Griffith Anderson