Flagship Pioneering Innovations Vi, LLC

Massachusetts Institute of Technology

Boston University

Robert James Citorik

Barrett Ethan Steinberg

William Edward Salomon

Jacob Rosenblum Rubens

Zi Jun Wang

Timothy Kuan-Ta Lu

Anne Helen Bothmer

Robert Charles Altshuler

Randi Michelle Kotlar

Nathaniel Roquet

Cecilia Giovanna Silvia Cotta-Ramusino

Ananya Ray

Kyusik Kim

Geoffrey Von Maltzahn

James Joseph Collins

Russell-John Krom

Sandeep Kumar

Stephen Hoyt Cleaver

Donghui Li

Carlos Sanchez

Mark Kyle Mimee

Luciano Henrique Apponi

Daniel Raymond Chee

Aamir Mir

Gregory David McAllister

Zhan Wang

William Querbes

Methods and compositions for modulating a target genome are disclosed. This disclosure relates to novel compositions, systems and methods for altering a genome at one or more locations in a host cell, tissue or subject, in vivo or in vitro. In particular, the invention features compositions, systems and methods for inserting, altering, or deleting sequences of interest in a host genome.

Methods and compositions for modulating a genome

Methods and compositions for modulating a target genome are disclosed. The composition may comprise a first RNA encoding a polypeptide comprising a retrotransposase reverse transcriptase domain and a retrotransposase endonuclease domain. The composition may also comprise a second RNA comprising a sequence that binds the polypeptide and a heterologous object sequence. The composition may insert the sequence of the heterologous object sequence into a target DNA.

The disclosure provides, e.g., compositions, systems, and methods for targeting, editing, modifying, or manipulating a host cell's genome at one or more locations in a DNA sequence in a cell, tissue, or subject. Gene modifying systems for treating cystic fibrosis, e.g., in subjects having a mutation resulting in F508del, are described.

CFTR-modulating compositions and methods

Methods and compositions for modulating a target genome are disclosed.

Various aspects and embodiments of the present disclosure are directed to methods and compositions for functionalizing endogenous bacteria in vivo. The methods include delivering to endogenous bacterial cells a recombinant bacteriophage or phagemid that is engineered to contain at least one genetic circuit.

Functionalization of endogenous bacteria

Various aspects and embodiments of the invention are directed to methods and compositions for reversing antibiotic resistance or virulence in and/or destroying pathogenic microbial cells such as, for example, pathogenic bacterial cells. The methods include exposing microbial cells to a delivery vehicle with at least one nucleic acid encoding an engineered autonomously distributed circuit that contains a programmable nuclease targeted to one or multiple genes of interest.

Tuning microbial populations with programmable nucleases

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Somerville, MA, United States of America

Robert James Citorik