Transduction Enhancers Improve Safety of Gene Therapy

Data from the Laboratory of Prof. Hauber at the Heinrich Pette Institute – Leibniz Institute for Experimental Virology (HPI) in Hamburg has shown that transduction enhancers can improve the transduction procedure in gene therapy. Transduction enhancers increase the chances of success for blood-cell targeted gene therapies and fine-tune the number of gene copies entering hematopoietic stem cells (HSC), data shows. This helps to address heightened safety requirements set forth by regulatory institutions.

In the absence of transduction enhancers, the low susceptibility of hematopoietic stem cells necessitates a high dose of lentivirus to even reach just a fraction of cells within the entire pool. While solid overexpression of gene elements can be advantageous for a number of therapeutic approaches, many vector strategies require a more refined approach. This is especially true for stem cells that may undergo several stages of proliferation and differentiation, making them highly susceptible to uncontrolled selection events.

Data from the Laboratory of Prof. Hauber demonstrates that standard methods for transduction of hematopoietic stem cells frequently result in sub-optimal efficiencies. The research of Prof. Hauber and his team focusses on innovative antiviral gene therapy strategies to actively remove HIV genes from blood cells and to establish long-lasting resistance against the viral intruder.

In this context they were searching for a method to improve the transduction procedure that is also transferrable to a future clinical setting. When the team added LentiBOOST transduction enhancer to the transduction protocol they perceived two effects.

• First, the fraction of transduction positive cells within the cell pool was significantly increased up to 80%.
• Second, the number of vector copies per diploid genome was between 3 and 5, an near-ideal value.

“These qualities are very helpful to fine-tune the effects of therapeutically relevant vectors that, if unchecked, could cause undesired effects. Optimizing transduction rate and at the same time limiting vector integration numbers to these levels means improving both, safety and chance of success for future gene therapies.” - Prof. Hauber commented.

LentiBOOST can be licensed from SIRION Biotech, Munich for applications in clinical R&D. As world leading innovator of viral vector technologies the company also maintains projects to improve AAV dependent applications and is actively developing a new AV serotype that is applicable in vaccination and immune oncology.

SIRION Biotech is looking forward to discuss projects to develop and improve virus based technologies that address the needs of a growing medical field.