Abstract
Top of pageAbstract Previous efforts to deliver genes into multiple muscles relied on isolated vessel perfusion with pressure or pharmacological interventions to enforce vector spread. We have compared a number of AAV serotype vectors (AAV1, 2, 5, 6, 7 and 8) for their ability to deliver genes systemically into muscle and heart without additional interventions. Here we showed that, in neonatal mice, a single-dose of intraperitoneal or intravenous administration of AAV vectors, particularly the AAV8 vector, led to efficient, systemic, and prolonged transductions of skeletal and cardiac muscles into adulthood. Additionally, intravenous injection of AAV8 in adult mice also achieved systemic muscle gene delivery, although the efficiency was lower than that of the neonatal mice. Long term and highly efficient gene transfer was also observed in non-muscle tissues, such as the liver, pancreas and the interstitial tissues of testis. In addition to mice, we further showed effectiveness of the AAV8 vector in both adult and neonatal hamsters. Compared to AAV8, AAV1 and AAV6, though robust in directly infecting skeletal muscle, were less effective in achieving systemic skeletal and cardiac muscle delivery after intravenous and intraperitoneal injection in both neonatal mice and adult mice. Finally, direct perfusion of isolated hind limb without high pressure via blood vessel in adult mice and hamsters suggested that AAV8 is more efficient in crossing the blood vessel barrier in muscle tissues than other vectors, suggesting potential mechanisms for the superiority of AAV8 vector in systemic gene delivery to striated muscles.
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