Provided herein are compositions that include at least two different nucleic acid vectors, where each of the at least two different vectors includes a coding sequence that encodes a different portion of an otoferlin protein, and the use of these compositions to treat hearing loss in a subject.

A single plasmid vector system for packaging recombinant human adenovirus type 4. The vector system contains an E3 region-deleted human adenovirus type 4 (HAdV-4 or Ad4) genome, a vector sequence for amplifying plasmids in bacteria, a pBR322 replication origin, a kanamycin resistance gene, and a replication control sequence; and an exogenous gene embedding site is located behind a packaging signal of the human adenovirus type 4 and in front of an E1 region. The present invention further provides a method for packaging the recombinant human adenovirus type 4 by the single plasmid vector system and an application in vaccine and drug preparation. The vector system can be used for rapidly and efficiently preparing a human adenovirus type 4 vector recombinant virus for stably expressing an exogenous gene, and has a good application prospect in the fields of preparation of a diagnostic kit, a vaccine, a gene therapy kit and/or a tumor therapy drug, etc.

Modified E1a regulatory sequences are provided, wherein at least one Pea3 binding site, or a functional portion thereof, is deleted. Also provided are modified E1a sequences that selectively express particular isoforms. Also provided is an E1b-19K clone insertion site. These modified sequences can be used individually, or in combination with one another, to provide tumor-selective expression of proteins.

Modified E1a regulatory sequences are provided, wherein at least one Pea3 binding site, or a functional portion thereof, is deleted. Also provided are modified E1a sequences that selectively express particular isoforms. Also provided is an E1b-19K clone insertion site. These modified sequences can be used individually, or in combination with one another, to provide tumor-selective expression of proteins.

Provided is a modified virus Ad5 which is capable of expressing a cytokine, and the modified virus Ad5 is capable of expressing an A20. And also provided are a vector and a cell comprising the modified virus Ad5. The modified virus may be used in cancer treatment.

Provided is a modified virus Ad5 which is capable of expressing a cytokine, and the modified virus Ad5 is capable of expressing an A20. And also provided are a vector and a cell comprising the modified virus Ad5. The modified virus may be used in cancer treatment.

Disclosed are compositions and methods for treating diseases of the mammalian eye, and in particular, complications of the retina associated with Usher syndrome IB (USH1B). Further disclosed are compositions and methods for treating diseases of the mammalian inner ear, and in particular, complications of ear hair cells associated with Usher syndrome IB (USH1B). The disclosure provides improved AAV-based, dual vector systems that facilitate the expression of full-length proteins whose coding sequences exceed that of the polynucleotide packaging capacity of an individual AAV vector. Described herein are modified hybrid dual vector systems that shift the coding sequence for the MY07A tail domain from the front-half vector to the back-half vector by altering the split point (e.g., from between exons 23 and 24, to between exons 21 and 22), in order to eliminate the production of truncated MY07A protein. Further described herein are improved, codon-modified hybrid and overlap vector systems in which putative stop codons and residual sequences in non-coding sequences are removed.

Provided are methods and compositions for treating cancer with a combination of neural stem cells (NSCs) and an oncolytic virus or a combination of oncolytic virotherapy and immune modulation. The method entails administrating to a subject a pharmaceutical composition comprising a combination of NSCs and an oncolytic virus, and/or NSCs packaged with one or more immunomodulatory viruses expressing one or more immunity checkpoint inhibitors, including adaptive immunity checkpoint inhibitors and innate immunity checkpoint inhibitors. The immunity checkpoint inhibitors include shRNAs against the immunity checkpoint proteins. The cancer includes but is not limited to primary, recurrent, and metastatic brain cancer, breast cancer, head and neck cancer, bladder cancer, ovarian cancer, uterine cancer, prostate cancer, skin cancer, lung cancer, and colorectal cancer.

Provided are methods and compositions for treating cancer with a combination of neural stem cells (NSCs) and an oncolytic virus or a combination of oncolytic virotherapy and immune modulation. The method entails administrating to a subject a pharmaceutical composition comprising a combination of NSCs and an oncolytic virus, and/or NSCs packaged with one or more immunomodulatory viruses expressing one or more immunity checkpoint inhibitors, including adaptive immunity checkpoint inhibitors and innate immunity checkpoint inhibitors. The immunity checkpoint inhibitors include shRNAs against the immunity checkpoint proteins. The cancer includes but is not limited to primary, recurrent, and metastatic brain cancer, breast cancer, head and neck cancer, bladder cancer, ovarian cancer, uterine cancer, prostate cancer, skin cancer, lung cancer, and colorectal cancer.

Mesenchymal stem cells for use as vehicles for therapeutic agents. The present invention is related to a method for selecting or obtaining mesenchymal stem cells (MSCs) that can be used as transporters or vehicles for therapeutic agents, especially in cancer treatment.