UCLA researchers in the Department of Microbiology, Immunology, and Molecular Genetics have developed a novel gene therapy vector identifying method, capable of screening toxicities of combination therapies.
TITLE:
A Method to Distinguish Different Retroviral Vectors During Integration Site Analysis
BACKGROUND:
Many diseases originate from defective genes or lack of defense mechanisms. To treat these diseases, the introduction of a synthetic gene to counter the defective or benign sequence can potentially stop or reverse these disease characteristics. Such a method relies on viral entities that can integrate their DNA into host cells. However, this process suffers from non-specific integration of a vector and could lead to abnormal behavior of host cells. To monitor in vivo clonal behavior of gene-modified cells, the integration site (IS) of vectors is used as marker to identify and track individual cell clones. Existing IS methods cannot distinguish between the IS of multiple therapeutic vectors, which is becoming an increasingly important feature in gene therapies. Next generation sequencing is the gold standard for this type of simultaneous analysis but detecting the IS of multiple vectors is still not possible at accurate levels. Therefore, there exists a need to be able to determine the IS of multiple vectors to evaluate the relative efficacy of different therapeutic vectors used in combination gene therapy.
INNOVATION:
Researchers at UCLA have developed a novel method that can distinguish the IS of different lentiviral vectors during integration site analysis. The method is capable of distinguishing therapeutic vectors from other viruses such as HIV-1. This first in class invention therefore allows assessment of each vector used in a combination gene therapy.
POTENTIAL APPLICATIONS:
• The identification of gene integration sites for multiple therapeutic viral vectors
• The identification of therapeutic viral vector in the presence of host viral vector (HIV-1)
ADVANTAGES:
• Can be integrated in the process of high throughput sequencing
• Technique is easily adopted into pre-existing vector modalities
DEVELOPMENT-TO-DATE:
The invention has been tested and validated.