University of Massachusetts

Zuoshang Xu

Guangping Gao

Hongwei Zhang

Hongyan Wang

Gregory Babcock

Teresa J Broering

Donna Ambrosino

Tariq M Rana

Thoru Pederson

Shaojie Zhang

Ardalan Naseri

Hanhui Ma

Xugang Xia

Maximilaan Huisman

Tu Li-Chung

Chunxing Yang

The invention in some aspects relates to recombinant adeno-associated viruses useful for targeting transgenes to CNS tissue, and compositions comprising the same, and methods of use thereof. In some aspects, the invention provides methods and compositions for treating CNS-related disorders.

CNS targeting AAV vectors and methods of use thereof

The present invention features anti-SOD1 antibodies and methods of using the antibodies for the treatment of amyotrophic lateral sclerosis (ALS) or the amelioration of symptoms associated with ALS.

Anti-SOD1 antibodies and uses thereof

Human diseases caused by dominant, gain-of-function mutations develop in heterozygotes bearing one mutant and one wild-type copy of a gene. Because the wild-type gene often performs important functions, whereas the mutant gene is toxic, any therapeutic strategy must selectively inhibit the mutant while retaining wild-type gene expression. The present invention includes methods of specifically inhibiting the expression of a mutant allele, while preserving the expression of a co-expressed wild-type allele using RNAi, a therapeutic strategy for treating genetic disorders associated with dominant, gain-of-function gene mutations. The invention also includes small interfering RNAs (siRNAs) and small hairpin RNAs (shRNAs) that selectively suppress mutant, but not wild-type, expression of copper zinc superoxide dismutase (SOD1), which causes inherited amyotrophic lateral sclerosis (ALS). The present invention further provides asymmetric siRNAs and shRNAs with enhanced efficacy and specificity and mediating RNAi.

Allele-specific RNA interference

The present invention relates to novel methods for treating dominant gain-of-function diseases. The invention provides methods for targeting regions of the copper zinc superoxide dismutase (SOD1), which causes inherited amyotrophic lateral sclerosis (ALS), with RNAi agent. The invention further provides RNAi resistant replacement genes containing mismatches with their respective RNAi agents. The invention also provides for vectors that express RNAi agent and RNAi resistant replacement gene of the present invention.

Methods and compositions for treating gain-of-function disorders using RNA interference

The invention features chemically modified small interfering RNAs (siRNAs) that are stable in vivo and retain the ability to form an A-form helix when in association with a target RNA. The features siRNA are effective therapeutics, particularly for targeting SOD1.

RNA interference agents for therapeutic use

Human diseases caused by dominant, gain-of-function mutations develop in heterozygotes bearing one mutant and one wild-type copy of a gene. Because the wild-type gene often performs important functions, whereas the mutant gene is toxic, any therapeutic strategy must selectively inhibit the mutant while retaining wild-type gene expression. The present invention includes methods of specifically inhibiting the expression of a mutant allele, while preserving the expression of a co-expressed wild-type allele using RNAi, a therapeutic strategy for treating genetic disorders associated with dominant, gain-of-function gene mutations. The invention also includes small interfering RNAs (siRNAs) and small hairpin RNAs (shRNAs) that selectively suppress mutant, but not wild-type, expression of copper zinc superoxide dismutase (SOD1), which causes inherited amyotrophic lateral sclerosis (ALS). The present invention further provides asysmmetric siRNAs and shRNAs with enhanced efficacy and specificity and mediating RNAi.

The present invention relates to novel methods for treating dominant gain-of-function diseases. The invention provides methods for targeting regions of the copper zinc superoxide dismutase (SOD1), which causes inherited amyotrophic lateral sclerosis (ALS), with RNAi agent. The invention further provides RNAi resistant replacement genes containing mismatches with their respective RNAi agent s. The invention also provides for vectors that express RNAi agent and RNAi resistant replacement gene of the present invention.

Growing community of inventors

Wellesley, MA, United States of America

Zuoshang Xu