The TAT Protein Transduction Domain as an Intra-Articular Drug Delivery Technology

Objective Intra-articular drug delivery holds great promise for the treatment of joint diseases such as osteoarthritis. The objective of this study was to evaluate the TAT peptide transduction domain (TAT-PTD) as a potential intra-articular drug delivery technology for synovial joints. Design Experiments examined the ability of TAT conjugates to associate with primary chondrocytes and alter cellular function bothin vitroandin vivo. Further experiments examined the ability of the TAT-PTD to bind to human osteoarthritic cartilage. Results The results show that the TAT-PTD associates with chondrocytes, is capable of delivering siRNA for chondrocyte gene knockdown, and that the recombinant enzyme TAT-Cre is capable of inducingin vivogenetic recombination within the knee joint in a reporter mouse model. Last, binding studies show that osteoarthritic cartilage preferentially uptakes the TAT-PTD from solution. Conclusions The results suggest that the TAT-PTD is a promising delivery strategy for intra-articular therapeutics.