Application of a Fas ligand encoding a recombinant adenovirus vector for prolongation of transgene expression

Area of Science:

• Immunology
• Gene Therapy
• Virology

Background:

• Adenovirus vectors are promising for gene therapy but face challenges with immunogenicity.
• Modulating the immune response is crucial for successful in vivo gene transfer.
• Fas ligand (FasL) plays a role in immune regulation and apoptosis.

Purpose of the Study:

• To investigate if ectopic expression of murine Fas ligand (mFasL) from an adenovirus vector can create an immunoprivileged site.
• To assess the impact of mFasL expression on adenovirus vector immunogenicity and transgene persistence.

Main Methods:

• Development of an adenovirus vector encoding mFasL under inducible control.
• In vivo administration of the vector to murine livers.
• Evaluation of cellular infiltration and transgene expression duration.

Main Results:

• Ectopic mFasL expression in murine livers induced inflammatory cellular infiltration.
• Myocyte-specific mFasL expression did not lead to prolonged vector-mediated transgene expression.
• The presence of functional mFasL did not establish an immunoprivileged site.

Conclusions:

• Ectopic expression of functional mFasL alone is insufficient to overcome adenovirus vector immunogenicity.
• Inflammatory responses and limited transgene persistence were observed despite mFasL expression.
• Strategies to mitigate adenovirus vector immunogenicity require further investigation beyond Fas ligand expression.