University of Massachusetts

Apellis Pharmaceuticals, Inc.

Christian Mueller

Robert H Brown, Jr

Terence Flotte

Phillip D Zamore

Neil Aronin

Edith L Pfister

Lukas Scheibler

Florie Borel

Scot Andrew Wolfe

Oliver King

Abbas Abdallah

Dongsheng Guo

Charles P Emerson

Gabriela Toro Cabrera

Sneha Suresh

Sukanya Iyer

Jennifer Chen

Phillip David Zamore

Heinz Francke

Paul Bergstrom

The disclosure provides, in some aspects, compositions (e.g., isolated nucleic acids and rAAVs) comprising a transgene which encodes at least one inhibitory nucleic acid which decreases expression of a gene encoding a serine palmitoyltransferase protein (e.g., SPTLC1). In some aspects, the disclosure relates to methods of treating hereditary sensory and autonomic neuropathy 1 (HSAN1) by administering the compositions described by the disclosure to a cell or subject.

Modulation of SPTLC1 via recombinant adeno-associated vectors

The present invention is directed to the filed of gene therapy. In particular, compositions and methods are disclosed that repair gene microduplication mutations by reversion to a wild type sequence. For example, the creation of a double stranded break by a programmable nuclease protein within a microduplication induces the microhomology mediated end joining DNA repair pathway that in the process of DNA repair removes the microduplication mutation and restores the wild type sequence.

Microhomology mediated repair of microduplication gene mutations

In some aspects, the disclosure relates to compositions and methods useful for inhibiting SOD1 expression in cells (e.g., cells of a subject). In some embodiments, the disclosure describes isolated nucleic acids engineered to express an inhibitory nucleic acid targeting endogenous SOD1 and an mRNA encoding a hardened SOD1 protein. In some embodiments, compositions and methods described by the disclosure are useful for treating Amyotrophic Lateral Sclerosis (ALS) in a subject.

SOD1 dual expression vectors and uses thereof

RNAs, such as miRNA and siRNA, and their use in treating complement-mediated disorders, are described.

RNAS for complement inhibition

The invention relates to isolated nucleic acids and rAAV-based compositions, methods and kits useful for treating genetic diseases (e.g., alpha-1 antitrypsin deficiency).

RAAV-based compositions and methods

Aspects of the disclosure relate to recombinant gene editing complexes comprising a recombinant gene editing protein and guide RNA (gRNA) that specifically hybridizes to a region of a C90RF72 gene (e.g., a region flanking a GCrepeat or within a exonic region of the gene).

Methods of treating amyotrophic lateral sclerosis (ALS)

Aspects of the disclosure relate to compositions and methods useful for treating Huntington's disease. In some embodiments, the disclosure provides interfering nucleic acids (e.g., artificial miRNAs) targeting the huntingtin gene (HTT) and methods of treating Huntington's disease using the same.

AAV treatment of Huntington's disease

The invention relates to inhibitory nucleic acids and rAAV-based compositions, methods and kits useful for treating Amyotrophic Lateral Sclerosis.

RAAV-based compositions and methods for treating amyotrophic lateral sclerosis

RNAs for complement inhibition

Transgenic non-human animals, e.g., rodents, e.g., mice comprising genomic mutations that inactive all of the serpin1A genes and thus lack any functional serpinA1 genes. As a result of the genomic mutations, the animals express no hepatic or circulatory AAT protein. Also provided herein are cells and tissues derived from the transgenic mice.

Growing community of inventors

Concord, MA, United States of America

Christian Mueller