Boston University

The General Hospital Corporation

Wilson W Wong

John T Ngo

Elliot Parker Tague

Huishan Li

Benjamin Harris Weinberg

Meng Lai Nicole Wong

Mark W Grinstaff

Jack R Kirsch

Curtis L Cetrulo

Eric M Bressler

Mohammadreza Pakyari

Atsushi Okuma

Jang Hwan Cho

Joshua Edward Mcgee

Lidya Yidnekachew Sertse

Kexin Li

The technology described herein relates to controlled chemically- or light-induced rejoinder of split-recombinases. In some embodiments, compositions, methods, kits and systems are provided that relate to a split-recombinase system, whereby protein complementation or rejoinder of split-recombinases is mediated by chemical-induced dimerization domains (CIDDs) or light-induced dimerization domains (LIDD) and rejoinder of the split-recombinases occur in the presence of one or more chemical inducers or light inducers, respectively. The split-recombinases systems as disclosed herein can be used in gene therapy, integrated logic and memory in living cells such as mammalian cells. The nucleic acid cassettes, switches, and systems described herein allow for controlled gene expression or gene regulation. The controlled chemically- or light-induced rejoinder of split-recombinases can be used in, for example, adopted T-cell therapy.

Inducible dimerization of recombinases

The technology described herein is directed to CAR polypeptides and systems comprising repressible proteases. In combination with a specific protease inhibitor, the activity of said CAR polypeptides and systems and cells comprising them can be modulated. Also described herein are methods of using said CAR polypeptides and systems, for example to treat various diseases and disorders.

Chimeric antigen receptor (CAR) modulation

The technology described herein is directed to compositions and methods for modifying and controlling the activity of cells by expression of proteins from self-amplifying RNA (saRNA). Also described herein are compositions and methods for modifying and controlling the activity of cells by expression of proteins from self-amplifying RNA that is substituted with chemically modified nucleotides.

Self-replicating RNA and uses thereof

The technology described herein is directed to compositions comprising components of multi-component CALs or CARs, e.g., a TCR recognition domain; and one or both of: (a) an intracellular signaling domain; and (b) a first-type protein interaction domain. Further provided herein are methods for treating or preventing an autoimmune disease, a transplant rejection, or graft versus host disease.

CAL-T constructs and uses thereof

Described herein is a chimeric antigen receptor (CAR) platform with the ability to (a) serve as an ON/OFF switch (with the ability for tenability/titrability), (b) sense multiple antigens and perform logic computations, and/or (c) independently regulate multiple signaling pathways. The compositions provided herein permit the degree of control and discrimination necessary to optimize CAR T cell therapy. Also described herein are cells comprising such compositions and the use of these compositions and/or cells in the treatment of cancer.

Methods and compositions relating to chimeric antigen receptors

The invention provides, inter alia, recombinase-based systems that provide for integrated logic and memory in living cells such as mammalian cells. The nucleic acid cassettes, switches, and systems described herein allow for control of gene expression or gene regulation. The invention also provides nucleic acid-based switches for adopted T-cell therapy.

DNA recombinase circuits for logical control of gene expression

Growing community of inventors

Brookine, MA, United States of America

Wilson W Wong