Prostate-targeting adeno-associated virus serotype vectors
Patent Number: WO2017070516
Executive Summary:
General Description:
Three types of prostate diseases are the major threats for the health of prostate, i.e., prostatitis, benign prostate hyperplasia (BPH) and prostate cancer. Together, these prostate diseases are severely compromising the life quality and life span of males, especially for the aged male population. To date, many efforts have been made to prevent or to treat prostate diseases, including surgery, medication, and radiotherapy. Nevertheless, highly effective clinical interventions for a variety of prostate diseases are still lacking. For example, although the early stage of prostate cancer can be prevented with hormonal therapy, most hormone-dependent prostate cancers will eventually develop into castration-resistant prostate cancer (CRPC). So far, no effective treatment exists for CRPC. As the genetic basis of prostate diseases was gradually unraveled during the past decades, gene therapy was explored as a therapeutic strategy for prostate diseases, and researchers have demonstrated the feasibility of several gene therapy approaches to treating BPH and prostate cancer in mice using various types of viral gene delivery vectors. However, many viral vectors, such as adenovirus, lentivirus and retrovirus, can cause insertional genotoxicity and/or immunotoxicity, which greatly limits their clinical use.
Adeno-associated virus (AAV) is a single-stranded DNA virus, and recombinant AAV (rAAV) vectors possess many advantages in gene therapy applications, including low immunogenicity and genotoxicity, broad tissue tropism and high transduction efficiency in vivo, and long-term transgene expression. Investigators at the University of Massachusetts Medical School recently made a discovery that rAAV vectors comprising capsid proteins having a certain serotype, including, but not limited to, AAV5, AAV6.2, AAV7, AAV8, AAV9, AAVrh. lO, mediate delivery of transgenes to prostate tissue more efficiently than other vectors (e.g., rAAV vectors comprising other capsid protein serotypes).
Strengths:
Weaknesses:
Patent Status:
Inventor Bio: Guangping Gao
https://profiles.umassmed.edu/display/129927
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: Publication date: Apr 27, 2017
- Patent: WO2017070516
- Link: https://www.google.com/patents/WO2017070516
- Research Institute: University of Massachusetts Medical School
- Disease Focus: Prostate disease (e.g., prostatitis, BPH, prostate cancer)
- Basis of Invention: Adeno-associated virus (AAV) is a single-stranded DNA virus, and recombinant AAV (rAAV) vectors possess many advantages in gene therapy applications, including low immunogenicity and genotoxicity, broad tissue tropism and high transduction efficiency in vivo, and long-term transgene expression
- How it works: Administering to a subject having or suspected of having a prostate disease an effective amount of rAAV, wherein the rAAV comprises (i) a capsid protein having a serotype selected from the group consisting of AAV5, AAV6.2, AAV7, AAV8, AAV9, and AAVrh.10, and (ii) a nucleic acid comprising a promoter operably linked to a transgene. Transgene encodes a gene associated with a prostate disease (i.e. a tumor suppressor molecule or miR34a)
- Lead Challenge Inventor: Guangping Gao
- Inventors: Guangping Gao, Jianzhong AI, Hong Li, Qiang Wei
- Development Stage: In vivo (mice)
- Novelty: rAAV vectors comprising capsid proteins mediate delivery of transgenes to prostate tissue more efficiently than other vectors
- Clinical Applications: Treatment of prostate disease (e.g., prostatitis, BPH, prostate cancer)
General Description:
Three types of prostate diseases are the major threats for the health of prostate, i.e., prostatitis, benign prostate hyperplasia (BPH) and prostate cancer. Together, these prostate diseases are severely compromising the life quality and life span of males, especially for the aged male population. To date, many efforts have been made to prevent or to treat prostate diseases, including surgery, medication, and radiotherapy. Nevertheless, highly effective clinical interventions for a variety of prostate diseases are still lacking. For example, although the early stage of prostate cancer can be prevented with hormonal therapy, most hormone-dependent prostate cancers will eventually develop into castration-resistant prostate cancer (CRPC). So far, no effective treatment exists for CRPC. As the genetic basis of prostate diseases was gradually unraveled during the past decades, gene therapy was explored as a therapeutic strategy for prostate diseases, and researchers have demonstrated the feasibility of several gene therapy approaches to treating BPH and prostate cancer in mice using various types of viral gene delivery vectors. However, many viral vectors, such as adenovirus, lentivirus and retrovirus, can cause insertional genotoxicity and/or immunotoxicity, which greatly limits their clinical use.
Adeno-associated virus (AAV) is a single-stranded DNA virus, and recombinant AAV (rAAV) vectors possess many advantages in gene therapy applications, including low immunogenicity and genotoxicity, broad tissue tropism and high transduction efficiency in vivo, and long-term transgene expression. Investigators at the University of Massachusetts Medical School recently made a discovery that rAAV vectors comprising capsid proteins having a certain serotype, including, but not limited to, AAV5, AAV6.2, AAV7, AAV8, AAV9, AAVrh. lO, mediate delivery of transgenes to prostate tissue more efficiently than other vectors (e.g., rAAV vectors comprising other capsid protein serotypes).
Strengths:
- Addition of the capsid protein and better delivery
Weaknesses:
- Has not been reproduced yet
Patent Status:
- Priority date: 2015-10-22
- Application date: 2017-04-27
Inventor Bio: Guangping Gao
https://profiles.umassmed.edu/display/129927
