Massachusetts Institute of Technology

Moderna Therapeutics, Inc.

The Ohio State University

Princeton University

Janssen Vaccines & Prevention B.v.

Other

Harvard College

Kyoto University

Raytheon Bbn Technologies Corp.

Modernatx, Inc.

Inria (french Institute for Research in Computer Science and Automation)

Ron Weiss

Darrell J Irvine

Antonin De Fougerolles

Tirtha Chakraborty

Tasuku Kitada

Patrick Guye

Jin Huh

Yingzhong Li

Jonathan William Babb

Mariane Bandeira Melo

Thomas Knight

Giulio Alighieri

Ronald Vogels

Stephane Bancel

Karl Dane Wittrup

Yizhou Dong

Ihor R Lemischka

Susan Whoriskey

Ely Blanton Porter

Yinqing Li

Zhen Xie

Marijn Van Der Neut Kolfschoten

Christoph Schaniel

Noor Momin

Ross D Jones

Maria Hottelet Foley

Mohammad Reza Ebrahimkhani

Shuo Cory Li

Miles Miller

Priscilla E M Purnick

Liliana Wroblewska

Sayda Mahgoub Elbashir

James Joseph Collins

Jason P Schrum

Jeff Lynn Ellsworth

Xavier Duportet

Justin Guild

Yun Long Jiang

Atanu Roy

Kenechi Ejebe

Kristy M Wood

Hirohide Saito

Paul Hatala

Matthias John

Kei Endo

Yuan Zhang

Jacob Stuart Michael Beal

He Chen

Yaakov Benenson

Aaron Daniel Adler

Fusun Yaman-Sirin

Kevin James Lebo

Jan Lonzaric

Parisa Yousefpour

Casper Enghuus

Velia Siciliano

Jeremy Jonathan Gam

Gregory Batt

Weixi Liao

Katie Bodner

Adam Rubin

Priscilla Purnick

Caroline DeHart

Elvira Vitu

Jon Monk

Aparna Swaminathan

Tyler Wagner

Noah Justin Davidsohn

Jacob Becraft

Breanna E DiAndreth

The present disclosure relates to synthetic oncolytic viruses comprising a lipid nanoparticle comprising one or more types of lipid and a self-amplifying replicon RNA comprising a sequence that encodes an immunomodulatory molecule.

Synthetic oncolytic LNP-replicon RNA and uses for cancer immunotherapy

Provided herein are genetic circuits and cell state classifiers for detecting the microRNA profile of a cell. The cell state classifiers of the present disclosure utilize phosphorylation state of a transcription factor to control classifier output. Kinases and phosphatase pairs that function in phosphorylating or dephosphorylating the transcription factor are integrated into the circuit, their expression tuned by the presence of microRNAs of interest (e.g., in a cell). The genetic circuits and cell state classifiers may be used in various applications (e.g., therapeutic or diagnostic applications).

Phosphorylation-based miRNA sensor

The present disclosure, at least in part, relates to a miRNA based logic gate that comprises an engineered RNA carrier that comprises an nuclear export signal, a target site for a first miRNA and a pre-miRNA sequence for a second miRNA. Also provided by the disclosure are recombinant viruses (e.g., recombinant adeno-associated viruses (rAAV)) for delivery of the miRNA based logic gates.

MicroRNA-based logic gates and uses thereof

Provided herein are genetic circuits and cell state classifiers for detecting the microRNA profile of a cell. The cell state classifiers of the present disclosure are designed to incorporate multiple genetic circuits integrated together by transcriptional or translational control. Multiple inputs can be sensed simultaneously by coupling their detection to different portions of the genetic circuit such that the output molecule is produced only when the correct input profile of miRNAs is detected. The genetic circuits and cell state classifiers may be used in various applications (e.g., therapeutic or diagnostic applications).

High performance multi-input microRNA sensors and uses thereof

The disclosure provides methods for an in vitro evolution technique to identify and characterize mutations in the non-structural genes of an alphavirus replicon that increase the strength and persistence of expression of the replicon genome. Also provided herein are in vivo methods for administering to an animal model a mutated alphavirus replicon that codes for a gene of experimental or therapeutic interest in the subgenome of the alphavirus replicon. The mutations identified herein improve the therapeutic potential of self-replicating RNA, which may have implications for cancer immunotherapy and beyond, e.g., for vaccination or gene therapy.

Methods for in vitro evolution of constructs derived from viruses

Provided herein are engineered HSV-1 vectors comprising a modified HSV-1 genome. The engineered HSV-1 vectors can be used to deliver genetic circuits (e.g., up to 100 kb) to cells in vitro or in vivo. Methods of treating or diagnosing a disease (e.g., cancer) using the engineered HSV-1 vectors described herein are also provided.

Engineered Herpes Simplex Virus-1 (HSV-1) vectors and uses thereof

The present disclosure is related to an engineered nucleic acid encoding a post-poly A signal RNA 3' to a terminator for expression of protein, and/or non-coding RNA. Also provided herein are methods for reducing epigenetic silencing, genetic modification, transcriptional regulation of the engineered nucleic acid described herein.

Engineered post-poly A signal RNA and uses thereof

Genetic circuits have been developed to regulate behaviors of replicon RNA in responses to small molecules, which has broader applications, such as for quantitative expression of cargo genes, temporary expression of immunomodulatory cytokines or antigens for better cancer immunotherapy or vaccination, and for increased safety in use of self-replicating vectors or in combination with other viral-delivery vectors. Described herein are genetic circuits suitable for systems that either require a tight off state or a slow off state, which can serve for instance where either a kill switch or prolonged protein expression (e.g., of vaccine antigens) are needed.

Control of replication and transcription of self-replicating RNA in response to small molecules

Disclosed herein is a subgenomic promoter library derived from alphavirus. Also provided herein are methods of using the subgenomic promoters to produce antibodies and other molecules.

Mutant subgenomic promoter library and uses thereof

Compositions and methods are described for inducing an immune response against an immunogen in humans. The induced immune response is obtained by administering a heterologous prime-boost combination of an in vitro transcribed (IVT) self-replicating RNA (repRNA) and an adenovirus vector. The compositions and methods can be used to provide a protective immunity against a disease, such as a viral infection or a cancer, in humans.

Methods and compositions for heterologous repRNA immunizations

The present disclosure, at least in part, relates to an engineered RNA (e.g., microRNA and sgRNA), in the absence of an input signal, that is engineered to have a large enough energy gap between the formations of a first secondary structure, which is unrecognizable by an actuator, and a second secondary structure, which is recognizable by an actuator (e.g., Drosha and Cas protein).

Trans-activated functional RNA by strand displacement and uses thereof

Provided herein are genetic circuits and encoded RNA transcripts that produce an output molecule in response to an RNA cleavage event that removes a degradation signal. In some embodiments, the genetic circuits described herein may be used for detecting RNA cleaver activities (e.g., in a cell). Methods of using the genetic circuits described herein in diagnostic or therapeutic applications are also provided.

RNA cleavage-induced transcript stabilizer and uses thereof

Growing community of inventors

Newton, MA, United States of America

Ron Weiss