The use of DNAPK inhibitors increases the efficacy of Lentiviral vectors and decreases off-target effects. 

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B922
Abstract ID: 5519

Presenting Author:
Seana L Corbin , Surgical Research Fellow at Univ. of Arkansas for Med. Sci.

Abstract:

Lentiviral vectors are a powerful tool in many models to deliver genetic material to target cells. Many methods of developing gene therapy treatment for multiple human diseases rely on using viral vectors to deliver genetic material into target cells. While viral vectors are a powerful tool, their use is not without its limitations and hurdles. Work must be done to overcome these hurdles to improve the delivery and reliability of vector-based gene therapy mechanisms in a clinically relevant and affordable manner.

The primary objective of this study was to enhance the precision and efficacy of lymphocyte modification while minimizing the systemic spread of the vectors. This was achieved through the strategic inhibition of DNA-PK, a key enzyme in DNA repair, to facilitate effective gene integration into lymphocyte genomes. These vectors were administered through trans-splenic injection, a novel approach aimed at directly targeting the lymphocyte-rich environment of the spleen with concurrent DNA-PK inhibition.

The results were significant. We observed a markedly high level of gene transduction in splenocytes 30% of T lymphocytes with minimal off-target effects. Notably, there was a substantial reduction in the systemic spread of the vectors, which is a critical factor in mitigating potential side effects. The transduced lymphocytes demonstrated stable gene expression, indicating the success of this method in achieving persistent genetic modification.