The disclosure, in some aspects, relates to nucleic acids, compositions and kits useful for gene therapy with reduced immune response to transgene products.

The present invention relates to small interfering RNA (siRNA) molecules against the SOD1 gene, adeno-associated viral (AAV) vectors encoding siRNA molecules and methods for treating amyotrophic lateral sclerosis (ALS) using the siRNA molecules and AAV vectors.

Disclosed herein are peptide sequences capable of directing adeno-associated viruses (AAV) to target specific environments, for example the nervous system and the heart, in a subject. Also disclosed are AAVs having non-naturally occurring capsid proteins comprising the disclosed peptide sequences, and methods of using the AAVs to treat diseases.

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.

The present invention relates to adeno-associated viral (AAV) particles encoding siRNA molecules and methods for treating amyotrophic lateral sclerosis (ALS).

The present invention relates generally to methods and compositions for gene therapy and immunotherapy that activate gamma delta T-cells, and in particular, can be used in the treatment of various cancers and infectious diseases.

The present invention encompasses genetically-modified immune cells (and populations thereof) expressing a microRNA-adapted shRNA (shRNAmiR) that reduces the expression of a target endogenous protein. Methods for reducing the expression of an endogenous protein in an immune cell are also provided wherein the method comprises introducing a shRNAmiR that targets the endogenous protein. Using shRNAmiRs for knocking down the expression of a target protein allows for stable knockdown of expression of endogenous proteins in immune cells.

The present invention relates to a RNA molecule comprising a first ribozyme, a first ligation sequence, an effector molecule, a second ligation sequence, and a second ribozyme. Methods of producing circular RNA molecules and treatment methods are also disclosed.

The subject matter disclosed herein is generally directed to inhibition of XPR1 :KIDINS220-mediated phosphate export to treat cancer, in particular, ovarian and uterine cancers. The subject matter disclosed herein is also generally directed to determining cancer dependency on phosphate export by detecting the expression of SLC34A2. Compositions for inhibiting XPR1 :KIDINS220-mediated phosphate export are also described.

The disclosure, in some aspects, relates to nucleic acids, compositions and kits useful for gene therapy with reduced immune response to transgene products.