A retroviral vector system comprising a packaging vector and a transfer vector, and a method of using the vectors for gene therapy.

Gene therapy is a technique based on the idea that a genetic disorder can be treated by replacing a dysfunctional gene with a functional copy of that gene.  Currently, retroviral vectors and adenoviral vectors are most frequently used for gene therapy clinical trials.  Retroviral vectors provide long term gene expression and are capable of transferring genes into non-dividing cells, unlike their adenoviral counterparts.  However, retroviral vectors often suffer from weak viral titers and inefficient encapsidation of the therapeutic gene, detracting from their therapeutic value.  Thus, there is a need in the art for improved retroviral gene therapy vectors.

This technology family is directed to a retroviral vector system comprising a packaging vector and a transfer vector, and a method of using the vectors for gene therapy.  The packaging vector is the result of an HIV-2 lentiviral vector containing mutations in sequences surrounding a splice donor site within the packaging signal.  The transfer vector comprises mutations that render a splice donor site non-functional.  These mutations increase the viral titer and expression/encapsidation of the transgene, but without a corresponding increase in the packaging of viral RNA.  Thus, these vectors may address some of the pressing concerns with current gene therapy vectors systems.

Applications:

• Improved lentivirus based vector system with practical application in gene therapy/gene transfer
• Two vector system minimizes possibility of HIV infection
• Packaging vector is a result of HIV-2 Lentivirus vector
• Improved packaging and expression ability addresses current low viral titer problem

 Market:

• The only gene therapy product currently in the market was approved in China in 2004.
• The R&D market of gene therapy is projected to grow to several billion dollars in the next 5 years.

 

Development Status:

The technology is currently in the pre-clinical stage of development.

 

Publication:

SK Arya et al. Human immunodeficiency virus type 2 lentivirus vectors for gene transfer: expression and potential for helper virus-free packaging. Hum Gene Ther. 1998 Jun 10;9(9):1371-1380.  [PubMed abs]

 

• U.S. Patent No. 6,790,657 issued 14 Sep 2004, entitled “Lentivirus Vector System” (HHS Reference No. E-231-1998/0-US-03)
• U.S. Patent No. 7,226,780 issued 05 Jun 2007, entitled “Lentivirus Vector System” (HHS Reference No. E-231-1998/0-US-04)

 

Inventors:

Suresh K. Arya (NCI)

 

Licensees Sought:

Available for exclusive or non-exclusive licensing.