A mouse model for adenovirus gene delivery

Area of Science:

• Virology
• Molecular Biology
• Genetics

Background:

• Adenovirus (Ad) gene delivery relies on the Coxsackie adenovirus receptor (CAR) for cellular entry.
• CAR expression is limited in certain cell types, hindering widespread Ad-based gene therapy applications.
• A strategy to overcome CAR restriction is needed for efficient Ad-gene delivery systems.

Purpose of the Study:

• To generate and characterize a transgenic mouse model expressing a truncated human CAR.
• To evaluate the utility of CAR transgenic mice for enhanced adenovirus infection in vitro and in vivo.
• To assess the potential of these mice for functional genomics and gene therapy research.

Main Methods:

• Generation of transgenic mice expressing a truncated human CAR in all analyzed tissues.
• In vitro infection assays using Ad-vectors on various primary cells from CAR transgenic mice.
• In vivo administration of Ad-vectors via tail vein injection to assess tissue tropism and infection efficiency.
• Analysis of infected cell populations, including lymphoid, myeloid, endothelial cells, macrophages, and lymphocytes.

Main Results:

• CAR transgenic mice demonstrated efficient in vitro Ad infections in lymphoid, myeloid, and endothelial cells at low multiplicities.
• In vivo Ad-vector administration successfully infected macrophages, lymphocytes, and endothelial cells in CAR transgenic mice.
• Tail vein injection led to Ad-vector targeting in previously inaccessible tissues like the lung and brain capillaries.

Conclusions:

• CAR transgenic mice provide a valuable model for overcoming Ad receptor limitations in gene delivery.
• These mice facilitate efficient in vivo gene transfer into a broader range of cell types and tissues.
• CAR transgenic mice are promising tools for functional genomic studies, gene therapy efficacy testing, and generating easily transduced cells.