University of Massachusetts

The Johns Hopkins University

Kennedy Krieger Institute, Inc.

Sourav Roy Choudhury

Miguel Sena Esteves

Ana Rita Batista

Kathryn Rae Wagner

Jennifer Gifford Green

The disclosure in some aspects relates to recombinant adeno-associated viruses having distinct tissue targeting capabilities. In some aspects, the disclosure relates to gene transfer methods using the recombinant adeno-associated viruses. In some aspects, the disclosure relates to isolated AAV capsid proteins and isolated nucleic acids encoding the same.

Heterologous targeting peptide grafted AAVs

Aspects of the disclosure relate to barcoded chimeric adeno-associated virus (AAV) capsid libraries, chimeric capsids and related recombinant AAVs (rAAVs) identified using the libraries. Specifically, the chimeric AAV capsid libraries comprise a plurality of nucleic adds encoding AAV capsid proteins, wherein each nucleic acid (i) encodes a unique AAV capsid protein having distinct polypeptide regions of greater than six amino acids in length that are derived from at least two different AAV serotypes, and (ii) comprises a unique barcode sequence. Further disclosed are methods of preparing an AAV library and identifying AAV capsids tropic for a target tissue.

High efficiency library-identified AAV vectors

The disclosure relates, in some aspects, to adeno-associated virus capsid proteins isolated from an in vivo library and recombinant adeno-associated viruses (rAAVs) comprising the same. In some aspects, the disclosure relates to isolated nucleic acids encoding AAV capsid proteins isolated from an in vivo library. In some embodiments, rAAVs and compositions described by the disclosure are useful for delivery of one or more transgenes to the muscle-tissue of a subject.

AAV capsids identified by in vivo library selection

The disclosure relates, in some aspects, to compositions and methods for enhanced delivery of a transgene to the central nervous system (CNS) of a subject. In some embodiments, the transgene is delivered by recombinant AAV (rAAV). In some embodiments, the method of enhancing transgene delivery comprises administering a blood brain barrier (BBB)-crossing molecule (e.g., K16ApoE) and an rAAV comprising a transgene to a subject.

Method to enhance the efficiency of systemic AAV gene delivery to the central nervous system

The disclosure relates, in some aspects, to adeno-associated vims capsid proteins isolated from an in vivo library and recombinant adeno-associated viruses (rAAVs) comprising the same. In some aspects, the disclosure relates to isolated nucleic acids encoding AAV capsid proteins isolated from an in vivo library. In some embodiments, rAAVs and compositions described by the disclosure are useful for delivery of one or more transgenes to the muscle-tissue of a subject.

Growing community of inventors

Newton, MA, United States of America

Sourav Roy Choudhury