Non-viral Gene Delivery Methods for Bone and Joints.

Gantenbein, Benjamin; Tang, Shirley; Guerrero, Julien; Higuita-Castro, Natalia; Salazar-Puerta, Ana I; Croft, Andreas S.; Gazdhar, Amiq; Purmessur, Devina (2020). Non-viral Gene Delivery Methods for Bone and Joints. Frontiers in Bioengineering and Biotechnology, 8, p. 598466. Frontiers Media 10.3389/fbioe.2020.598466

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Viral carrier transport efficiency of gene delivery is high, depending on the type of vector. However, viral delivery poses significant safety concerns such as inefficient/unpredictable reprogramming outcomes, genomic integration, as well as unwarranted immune responses and toxicity. Thus, non-viral gene delivery methods are more feasible for translation as these allow safer delivery of genes and can modulate gene expression transiently both in vivo, ex vivo, and in vitro. Based on current studies, the efficiency of these technologies appears to be more limited, but they are appealing for clinical translation. This review presents a summary of recent advancements in orthopedics, where primarily bone and joints from the musculoskeletal apparatus were targeted. In connective tissues, which are known to have a poor healing capacity, and have a relatively low cell-density, i.e., articular cartilage, bone, and the intervertebral disk (IVD) several approaches have recently been undertaken. We provide a brief overview of the existing technologies, using nano-spheres/engineered vesicles, lipofection, and in vivo electroporation. Here, delivery for microRNA (miRNA), and silencing RNA (siRNA) and DNA plasmids will be discussed. Recent studies will be summarized that aimed to improve regeneration of these tissues, involving the delivery of bone morphogenic proteins (BMPs), such as BMP2 for improvement of bone healing. For articular cartilage/osteochondral junction, non-viral methods concentrate on targeted delivery to chondrocytes or MSCs for tissue engineering-based approaches. For the IVD, growth factors such as GDF5 or GDF6 or developmental transcription factors such as Brachyury or FOXF1 seem to be of high clinical interest. However, the most efficient method of gene transfer is still elusive, as several preclinical studies have reported many different non-viral methods and clinical translation of these techniques still needs to be validated. Here we discuss the non-viral methods applied for bone and joint and propose methods that can be promising in clinical use.

Item Type:

Journal Article (Review Article)

Division/Institute:

09 Interdisciplinary Units > Microscopy Imaging Center (MIC)
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Orthopaedic Surgery
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Services > Core Facility Zytometrie-Labor/FACSlab

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Gantenbein, Benjamin; Guerrero, Julien Paul; Croft, Andreas Shaun and Gazdhar, Amiq

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology
600 Technology > 620 Engineering
600 Technology > 660 Chemical engineering

ISSN:

2296-4185

Publisher:

Frontiers Media

Language:

English

Submitter:

Benjamin Gantenbein

Date Deposited:

30 Dec 2020 16:33

Last Modified:

10 Mar 2021 02:21

Publisher DOI:

10.3389/fbioe.2020.598466

PubMed ID:

33330428

Uncontrolled Keywords:

BMP2 FOXF1 GDF5 bone cartilage intervertebral disk non-viral gene delivery tendon

BORIS DOI:

10.48350/149902

URI:

https://boris.unibe.ch/id/eprint/149902

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