The TAT protein transduction domain as an intra-articular drug delivery technology
Mailhiot, Sarah E.; Thompson, Matthew A.; Eguchi, Akiko E.; Dinkel, Sabrina E.; Lotz, Martin K.; Dowdy, Steven F.; June II, Ronald K. (2020-09-20)
Mailhiot, S. E., Thompson, M. A., Eguchi, A. E., Dinkel, S. E., Lotz, M. K., Dowdy, S. F., & June, R. K. (2021). The TAT Protein Transduction Domain as an Intra-Articular Drug Delivery Technology. CARTILAGE, 1637S-1645S. https://doi.org/10.1177/1947603520959392
© 2020 SAGE Publications. The final authenticated version is available online at https://doi.org/10.1177/1947603520959392.
https://rightsstatements.org/vocab/InC/1.0/
https://urn.fi/URN:NBN:fi-fe2021081843624
Tiivistelmä
Abstract
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 both in vitro and in 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 inducing in vivo genetic 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.
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