TY - JOUR
T1 - Osteoarthritis gene therapy in 2022
AU - Evans, Christopher H.
AU - Ghivizzani, Steven C.
AU - Robbins, Paul D.
N1 - Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - Purpose of reviewTo assess the present status of gene therapy for osteoarthritis (OA).Recent findingsAn expanding list of cDNAs show therapeutic activity when introduced into the joints of animals with experimental models of OA. In vivo delivery with adenovirus or adeno-associated virus is most commonly used for this purpose. The list of encoded products includes cytokines, cytokine antagonists, enzymes, enzyme inhibitors, growth factors and noncoding RNA. Elements of CRISPR-Cas have also been delivered to mouse knees to ablate key genes. Several human trials have been initiated, using transgenes encoding transforming growth factor-β1, interleukin-1 receptor antagonist, interferon-β, the NKX3.2 transcription factor or variant interleukin-10. The first of these, using ex vivo delivery with allogeneic chondrocytes, gained approval in Korea which was subsequently retracted. However, it is undergoing Phase III clinical trials in the United States. The other trials are in Phase I or II. No gene therapy for OA has current marketing approval in any jurisdiction.SummaryExtensive preclinical data support the use of intra-articular gene therapy for treating OA. Translation is beginning to accelerate and six gene therapeutics are in clinical trials. Importantly, venture capital has begun to flow and at least seven companies are developing products. Significant progress in the future can be expected.
AB - Purpose of reviewTo assess the present status of gene therapy for osteoarthritis (OA).Recent findingsAn expanding list of cDNAs show therapeutic activity when introduced into the joints of animals with experimental models of OA. In vivo delivery with adenovirus or adeno-associated virus is most commonly used for this purpose. The list of encoded products includes cytokines, cytokine antagonists, enzymes, enzyme inhibitors, growth factors and noncoding RNA. Elements of CRISPR-Cas have also been delivered to mouse knees to ablate key genes. Several human trials have been initiated, using transgenes encoding transforming growth factor-β1, interleukin-1 receptor antagonist, interferon-β, the NKX3.2 transcription factor or variant interleukin-10. The first of these, using ex vivo delivery with allogeneic chondrocytes, gained approval in Korea which was subsequently retracted. However, it is undergoing Phase III clinical trials in the United States. The other trials are in Phase I or II. No gene therapy for OA has current marketing approval in any jurisdiction.SummaryExtensive preclinical data support the use of intra-articular gene therapy for treating OA. Translation is beginning to accelerate and six gene therapeutics are in clinical trials. Importantly, venture capital has begun to flow and at least seven companies are developing products. Significant progress in the future can be expected.
KW - cartilage
KW - clinical translation
KW - clinical trial
KW - intra-articular therapy
KW - synovium
KW - vector
UR - http://www.scopus.com/inward/record.url?scp=85144200813&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85144200813&partnerID=8YFLogxK
U2 - 10.1097/BOR.0000000000000918
DO - 10.1097/BOR.0000000000000918
M3 - Article
C2 - 36508307
AN - SCOPUS:85144200813
SN - 1040-8711
VL - 35
SP - 37
EP - 43
JO - Current opinion in rheumatology
JF - Current opinion in rheumatology
IS - 1
ER -