Key result
Intra-arterial rAAV efficiently delivers genes to rodent hind limbs with distinct expression patterns vs intra-muscular injection.
Femoral intra-arterial injection is an efficient and viable alternative to intra-muscular injection for delivering rAAV constructs to rodent hind limb muscles.
Hypothesis-generating for intra-arterial rAAV delivery in rodents; leaves open translation to larger models or humans.
With the aim of simplifying recombinant-adeno-associated virus (rAAV) delivery in muscle, a new femoral intra-arterial technique was designed and tested in rodents (rats and mice). Two serotypes, several promoters and transgenes (reporter or therapeutic) were tested using this administration route. The new route is both easy to perform and efficient. Its usefulness as a tool to assess gene delivery constructs in the muscle was established in the context of recombinant AAV serotypes 1 and 2, and with the ubiquitous CMV and two muscle-specific (C5-12 and CK6) promoters. Both serum monitoring of a secreted protein (murine alkaline phosphatase: muSEAP) and slide staining were used to compare the different constructs. Significantly different patterns of expression in kinetics of expression (muSEAP) and homogeneity of fiber transduction (staining) were evidenced with the different promoters tested, and compared with intra-muscular expression patterns. Detailed studies of differential transduction in leg and thigh muscles showed equivalent efficacy, except in rectus femoris, and to a lesser extent in soleus. In light of these results and prior data, intra-arterially mediated gene transfer mechanism is discussed.
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Gonin et al. (2005) studied Gene delivery in muscle. Femoral intra-arterial injection of rAAV vs. Intra-muscular injection was evaluated on Patterns of expression in kinetics of expression and homogeneity of fiber transduction. Femoral intra-arterial injection of rAAV in rodents provided an efficient route for gene delivery to hind limb muscles, showing different expression patterns compared to intra-muscular injection.
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