公开(公告)号：US20210047694A1

公开(公告)日：2021-02-18

申请号：US16995425

申请日：2020-08-17

申请人： The Broad Institute, Inc. ,  Massachusetts Institute of Technology ,  The Brigham and Women's Hospital, Inc. ,  The General Hospital Corporation

发明人： Aviv Regev ,  Nir Hacohen ,  Vijay K. Kuchroo ,  Ana Carrizosa Anderson ,  Orit Rozenblatt-Rosen ,  Jonathan Chen ,  Karin Pelka ,  Matan Hofree

IPC分类号： C12Q1/6886

摘要： The present invention is generally directed to a colorectal (CRC) cell atlas that provides methods of predicting outcomes of cancer patients and therapeutic targets for treating patients in need thereof. The atlas may be used to predict a response to immunotherapy, in particular checkpoint blockade therapy and adoptive cell transfer. Disclosed herein are previously unidentified gene programs in tumors that can be used to predict response and provide for therapeutic targets that can be used to shift a tumor to a responsive phenotype.

公开(公告)号：US20240067957A1

公开(公告)日：2024-02-29

申请号：US18339607

申请日：2023-06-22

申请人： Massachusetts Institute of Technology ,  President and Fellows of Harvard College

发明人： James J. Collins ,  Raphael Gayet ,  Katherine IIia ,  Shiva Razavi ,  Nathaniel Tippens ,  Kehan Zhang ,  Jack Chen ,  Jonathan Chen ,  Makoto Lalwani

IPC分类号： C12N15/10 ,  C12N9/78 ,  C12N15/11 ,  C12N15/86

CPC分类号： C12N15/1082 ,  C12N9/78 ,  C12N15/1086 ,  C12N15/11 ,  C12N15/86 ,  C12Y305/04004 ,  C12N2310/20 ,  C12N2310/531 ,  C12N2750/14143

摘要： Genetic circuits that control transgene expression in response to pre-defined transcriptional cues would enable the development of smart therapeutics. The present disclosure relates to engineered programmable single-transcript RNA sensors in which adenosine deaminases acting on RNA (ADARs) autocatalytically convert trigger hybridization into a translational output. This system amplifies the signal from editing by endogenous ADAR through a positive feedback loop. Amplification is mediated by the expression of a hyperactive, minimal ADAR variant and its recruitment to the edit site via an orthogonal RNA targeting mechanism. This topology confers high dynamic range, low background, minimal off-target effects, and a small genetic footprint. The circuits and systems disclosed herein leverage an ability to detect single nucleotide polymorphisms and modulate translation in response to endogenous transcript levels in mammalian cells.