University of Oulu

Mailhiot, S. E., Thompson, M. A., Eguchi, A. E., Dinkel, S. E., Lotz, M. K., Dowdy, S. F., & June, R. K. (2020). The TAT Protein Transduction Domain as an Intra-Articular Drug Delivery Technology. CARTILAGE, 194760352095939. https://doi.org/10.1177/1947603520959392

The TAT protein transduction domain as an intra-articular drug delivery technology

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Author: Mailhiot, Sarah E.1; Thompson, Matthew A.2; Eguchi, Akiko E.3;
Organizations: 1University of Oulu, Oulu, Finland
2Montana State University, Bozeman, MT, USA
3Mie University, Tsu, Mie, Japan
4The Scripps Research Institute, La Jolla, CA, USA
5University of California, San Diego, La Jolla, CA, UsA 22 23
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 2.3 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021081843624
Language: English
Published: SAGE Publications, 2021
Publish Date: 2021-08-18
Description:

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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Series: Cartilage
ISSN: 1947-6035
ISSN-E: 1947-6043
ISSN-L: 1947-6035
Volume: In press
DOI: 10.1177/1947603520959392
OADOI: https://oadoi.org/10.1177/1947603520959392
Type of Publication: A1 Journal article – refereed
Field of Science: 217 Medical engineering
Subjects:
Copyright information: © 2020 SAGE Publications. The final authenticated version is available online at https://doi.org/10.1177/1947603520959392.