The invention provides a method for ameliorating chronic pain signaling involving transient receptor potential cation channel subfamily V member 1 (TRPV1) by expressing PP1 in neurons. The invention also provides HSV vectors for expressing PP1 within neurons and compositions comprising such vectors.

The invention provides viral vectors (e.g., herpes viral vectors) and methods of using these vectors to treat disease.

Provided herein are methods of delivering transgenes to an eye of a subject comprising the use of pharmaceutical compositions having one or more polynucleotides suitable for enhancing, increasing, augmenting, and/or supplementing the levels of the transgene in the eye. Also provided herein are methods of correcting vision loss in a subject in need thereof comprising the use of the pharmaceutical compositions described herein.

The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding a cystic fibrosis transmembrane conductance regulator (CFTR) polypeptide (e.g., a human CFTR polypeptide); viruses comprising the recombinant nucleic acids; compositions and formulations comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for the treatment of a chronic lung disease, such as cystic fibrosis); and articles of manufacture or kits thereof.

An obligate oHSV vector comprising modified viral DNA genome is provided. A recombinant oHSV-1 construct comprising the obligate oHSV vector and a heterologous nucleic acid sequence encoding an immunostimulatory and/or immunotherapeutic agent is also provided. Compositions comprising the recombinant oHSV-1 construct can be used for treating cancers.

Malignant tumors that are resistant to conventional therapies represent significant therapeutic challenges. An embodiment of the present invention provides a second generation oncolytic virus rQNestin34.5v2 with less toxicity that is more effective at selective killing target cells, such as tumor cells. In various embodiments presented herein, the oncolytic virus described herein is suitable for treatment of glioblastoma, as well as other cancers.

Disclosed herein are compositions and methods for treating neuropathy, embodiments, HSV vectors are provided comprising nucleic acid molecules encoding neurotrophins, such as neurotrophin 3 (NT3).

Provided herein are engineered HSV-1 vectors comprising a modified HSV-1 genome. The engineered HSV-1 vectors can be used to deliver genetic circuits (e.g., up to 100 kb) to cells in vitro or in vivo. Methods of treating or diagnosing a disease (e.g., cancer) using the engineered HSV-1 vectors described herein are also provided.

Provided herein, in some aspects, are antibody expression systems comprising DNA launched RNA replicons for high level antibody expression. In some embodiments, the antibody is a therapeutic antibody. In some embodiments, the antibody is an immune check point inhibitor. Methods of using the antibody expression system for treating diseases (e.g., cancer) are also provided.

Provided herein are compositions and methods for vaccination and research applications. In particular, provided herein are non-neuroinvasive herpesviruses and alpha herpesviruses and uses thereof.