Harvard College

Leland Stanford Junior University

Quan Lu

Stanley N Cohen

Qiyu Wang

Joseph F Nabhan

MINIMAL ARRESTIN DOMAIN CONTAINING PROTEIN 1(ARRDC1) CONSTRUCTS

Methods, systems, compositions and strategies for the delivery of WW domain-containing fusion proteins into cells in vivo, ex vivo, or in vitro via ARMMs are provided. Methods, systems, compositions and strategies for the delivery of Cas9 proteins and/or Cas9 variants into cells in vivo, ex vivo, or in vitro via fusion to ARMM associated proteins (e.g., ARRDC1 or TSG101) are also provided.

Delivery of CAS9 via ARRDC1-mediated microvesicles (ARMMs)

Methods, systems, compositions and strategies for the delivery of RNA into cells in vivo, ex vivo, or in vitro via ARMMs are provided. In some aspects, ARMMs containing fusion proteins of ARRDC1 fused to an RNA binding protein or an RNA binding protein fused to a WW domain are provided. In some aspects, ARMMs containing binding RNAs associated with cargo RNAs are provided. In other aspects, cargo RNAs associated with a binding RNA, such as a TAR element, are loaded into ARMMs via ARRDC1 fusion proteins containing an RNA binding protein, such as trans-activator of transcription (Tat) protein.

Delivery of therapeutic RNAs via ARRDC1-mediated microvesicles

Methods, systems, compositions and strategies for the delivery of WW domain-containing fusion proteins into cells in vivo, ex vivo, or in vitro via ARMMs are provided. Methods, systems, compositions and strategies for the delivery of cargo proteins into cells in vivo, ex vivo, or in vitro via fusion to ARMM associated proteins (e.g., ARRDC1 or TSG101) are also provided.

Delivery of cargo proteins via ARRDC1-mediated microvesicles (ARMMs)

The invention provide isolated arrestin domain-containing protein 1 (ARRDC1)-mediated microvesicles (ARMMs). Methods for generating and for isolating ARMMs are also provided herein. ARMMs can be used to deliver agents, for example, nucleic acids (e.g., siRNAs, microRNAs, lincRNAs), proteins (e.g., transcription factors, chromatin modulators, kinases, phosphorylases, or recombinases), or small molecules to target cells in vitro and in vivo, and methods for such ARMM-mediated delivery are provided herein. Diagnostic and therapeutic methods using ARMMs are also described herein.

ARRDC1-mediated microvesicles (ARMMS) and uses thereof

Methods, systems, compositions and strategies for the delivery of WW domain-containing fusion proteins into cells in vivo, ex vivo, or in vitro via ARMMs are provided. Methods, systems, compositions and strategies for the delivery of cargo proteins, such as transcription factors, tumor suppressors, developmental regulators, growth factors, metastasis suppressors, pro-apoptotic proteins, nucleases, recombinases, and reprogramming factors into cells in vivo, ex vivo, or in vitro via fusion to ARMM associated proteins (e.g., ARRDC1 or TSG101) are also provided.

The invention provide isolated arrestin domain-containing protein 1 (ARRDC1)-mediated micro vesicles (ARMMs). Methods for generating and for isolating ARMMs are also provided herein. ARMMs can be used to deliver agents, for example, nucleic acids (e.g., siRNAs, microRNAs, lincRNAs), proteins (e.g., transcription factors, chromatin modulators, kinases, phosphorylases, or recombinases), or small molecules to target cells in vitro and in vivo, and methods for such ARMM-mediated delivery are provided herein. Diagnostic and therapeutic methods using ARMMs are also described herein.

Growing community of inventors

Newton, MA, United States of America

Quan Lu