Non-viral Gene Therapy for Osteoarthritis.

Ilona Uzieliene,Ursule Kalvaityte,Eiva Bernotiene,Ali Mobasheri

doi:10.3389/fbioe.2020.618399

Abstract

Strategies for delivering nucleic acids into damaged and diseased tissues have been divided into two major areas: viral and non-viral gene therapy. In this mini-review article we discuss the application of gene therapy for the treatment of osteoarthritis (OA), one of the most common forms of arthritis. We focus primarily on non-viral gene therapy and cell therapy. We briefly discuss the advantages and disadvantages of viral and non-viral gene therapy and review the nucleic acid transfer systems that have been used for gene delivery into articular chondrocytes in cartilage from the synovial joint. Although viral gene delivery has been more popular due to its reported efficiency, significant effort has gone into enhancing the transfection efficiency of non-viral delivery, making non-viral approaches promising tools for further application in basic, translational and clinical studies on OA. Non-viral gene delivery technologies have the potential to transform the future development of disease-modifying therapeutics for OA and related osteoarticular disorders. However, further research is needed to optimize transfection efficiency, longevity and duration of gene expression.

Highlights

Osteoarthritis (OA) is a leading cause of disability across the world and a major cost contributor to health and social care systems (Hunter and Bierma-Zeinstra, 2019)
Acetaminophen is weakly recommended by ESCEO (Bruyère et al, 2019) and not recommended in the most recent Osteoarthritis Research Society International (OARSI) (Bannuru et al, 2019) and ACR (Kolasinski et al, 2020) treatment guidelines. These issues highlight the acute need for the development of newer and safer treatments for OA, placing greater emphasis on the necessity for understanding disease phenotypes, their underlying molecular endotypes and targeting the molecules and pathways associated with them (Mobasheri et al, 2019a,b; Van Spil et al, 2019)
Engineering mesenchymal stem cells (MSCs) that can attach to the ECM in cartilage was a concept that was tried and tested more than a decade ago (Robbins et al, 2003) but the emphasis appears to have shifted to modulating chondrocyte metabolism (Pirozzi et al, 2018), paracrine activity (Madry et al, 2004) and altering the inflammatory milieu of the microenvironment (Matta et al, 2015)

Summary

INTRODUCTION

Osteoarthritis (OA) is a leading cause of disability across the world and a major cost contributor to health and social care systems (Hunter and Bierma-Zeinstra, 2019). Official recommendations for OA treatment are often divided into non-pharmacological, pharmacological, and surgical interventions (Bijlsma et al, 2011; Buttgereit et al, 2015). In the absence of disease-modifying OA drugs (DMOADs), most clinical guidelines recommend the provision of education, physical therapy and weight management in their core treatment recommendations (Nelson et al, 2014). Gene Therapy for Osteoarthritis of biological drugs (Mobasheri, 2013a) and cell-based therapies (Salem et al, 2019; Grässel and Muschter, 2020). This concise mini review summarizes the most significant papers on advances of a non-viral gene delivery studies in OA. Advantages and disadvantages of different types of gene modifications for the treatment of OA are summarized and the future perspectives and directions of this rapidly developing field are reviewed

CURRENT THERAPEUTIC APPROACHES IN OA

CELL AND GENE THERAPY FOR OA

Viral Gene Transfer Systems for OA

FUTURE TRENDS AND PERSPECTIVES

Findings

AUTHOR CONTRIBUTIONS