Application of gene therapy in the treatment of superficial digital flexor tendon injury in horses

Aimaletdinov, Alexander; Mindubaeva, Gulnur; Khalikova, Svetlana; Kabwe, Emmanuel; Салмакова, А. В.; Alexandrova, Natalia; Rizvanov, Albert A.; Zakirova, Elena

doi:10.4314/ovj.v10i3.3

Cited by 10 publications

(8 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, although a combined effect of both VEGF164 and FGF2 was evaluated, Kovac et al (2018) found significant improvements in ultrasonographic and clinical in eight out of 10 horses with the superficial digital flexor tendon and suspensory ligament branch lesions (in naturally occurring tendinitis and desmitis in horses) with gene therapy using plasmid DNA encoding VEGF164 and FGF2 genes, returning to pre-injury level in 2–6 months. Similarly, the positive effects of plasmid DNA encoding VEGF164 and FGF2 genes were reported in two case reports ( Kovac et al, 2017 ; Aimaletdinov et al, 2020 ).…”

Section: The Role Of Exogenous Vascular Endothelial Growth Factor Delivery In Tendon Healingsupporting

confidence: 56%

“…Sodium hyaluronate, a good carrier of VEGF, could prolong the mean residence time to better play the biological role of VEGF ( Chen et al, 2012 ). Furthermore, gene delivery by adeno-associated virus (AAV) vectors or plasmid DNA encoding gene may also be effective way to deliver VEGF to the injured tendon ( Tang et al, 2016 ; Mao et al, 2017 ; Kovac et al, 2018 ; Aimaletdinov et al, 2020 ). Different delivery method may also affect the effect of exogenous VEGF in tendon healing.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Role of Vascular Endothelial Growth Factor in Tendon Healing

Liu

Zhu

et al. 2021

Front. Physiol.

View full text Add to dashboard Cite

Angiogenesis is crucial to facilitate tendon healing, such as delivering oxygen and nutrients, removing waste products, and controlling immune responses. Vascular endothelial growth factor (VEGF) is one of the most vital angiogenic factors that regulate blood vessel formation in tendon healing. Recently, biological therapies, including the application of exogenous VEGF, have been attracting increasing attention. However, at present, the effect of the application of exogenous VEGF in tendon healing is controversial, as the role of endogenous VEGF in tendons has also not been fully elucidated. This article will summarize the role of both endogenous and exogenous VEGF in tendon healing and discuss possible reasons for the controversy. The present review shows that tendon repair is facilitated only by proper angiogenesis and VEGF at the early stage, whereas the persistent high VEGF expression and prolonged presence of blood vessels may impair tendon repair at a later stage.

show abstract

Section: The Role Of Exogenous Vascular Endothelial Growth Factor Delivery In Tendon Healingsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

The Role of Vascular Endothelial Growth Factor in Tendon Healing

Liu

Zhu

et al. 2021

Front. Physiol.

View full text Add to dashboard Cite

show abstract

“…In addition, as the sequence length of the promoter and upstream additional sequence of the transgene are unknown, it is also difficult to predict the size of the PCR product. The former issue may be addressed by designing and preparing primers for multiple targeting, such as CMV and EF‐1 α as eukaryotic promoters (Aimaletdinov et al, 2020; Litvin et al, 2016). To solve the latter problem, it might be necessary to determine the sequence of the amplified PCR product.…”

Section: Discussionmentioning

confidence: 99%

Identification of processed pseudogenes in the genome of Thoroughbred horses: Possibility of gene‐doping detection considering the presence of pseudogenes

et al. 2022

View full text Add to dashboard Cite

Processed pseudogenes, also known as retrocopy genes, are copies of messenger RNAs that have been reverse transcribed into DNA and inserted into the genome. In this study, we identified 62 processed pseudogene candidates as intron‐less genes from whole‐genome sequencing (WGS) data of Thoroughbred horses using delly structural variation software. The 62 processed pseudogene candidates were confirmed by PCR amplification of intron‐less products. A total of 11 processed pseudogenes were confirmed in the genome of all 23 analysed horses, whereas three processed pseudogenes with structures of ATP11B, DPH3 and RPL17 were detected in only one of 115 horses by PCR amplification of intron‐less products. Currently, most of the gene doping tests proposed in human and horse sports are adapted PCR‐based methods using hydrolysis probes to detect exon/exon junctions in transgenes because the operation is simple and economical. However, when the pseudogene is present in the host genome, the PCR‐based methods may have a potential risk of detecting false positives. In this study, because processed pseudogenes that exist less frequently in the horse genome may affect PCR‐based transgene detection in gene‐doping tests, we propose and demonstrate that PCR amplification and sequencing using primers designed on transgene and promotors and/or polyadenylation signal for gene expression are useful for gene‐doping detection as an additional confirmatory test to prevent false positives.

show abstract

“…Lastly, a double‐blinded, placebo‐controlled study showed that intertumoral treatment with equine IL‐18 and IL‐12‐encoding pDNA resulted in significant tumor regression compared with placebo‐treated control patients 85 . Other applications of gene therapy in equine clinical patients involve pDNA encoding equine VEGF and FGF2 to promote healing of injured tendons and ligaments 16–18 . This gene therapy product was developed in Russia, 14 where it was approved for use in human patients 15 .…”

Section: Introductionmentioning

confidence: 99%

Administration and detection of gene therapy in horses: A systematic review

Haughan

Ortved

Robinson

2022

Drug Testing and Analysis

View full text Add to dashboard Cite

Gene therapy uses genetic modification of cells to produce a therapeutic effect.Defective or missing genes can be repaired or replaced, or gene expression can be modified using a variety of technologies. Repair of defective genes can be achieved using specialized gene editing tools. Gene addition promotes gene expression by introducing synthetic copies of genes of interest (transgenes) into cells where they are transcribed and translated into therapeutic proteins. Protein production can also be modified using therapies that regulate gene expression.Gene therapy is currently prohibited in both human and equine athletes because of the potential to induce production of performance-enhancing proteins in the athlete's body, also referred to as "gene doping." Detection of gene doping is challenging and necessitates development of creative, novel analytical methods for doping control. Methods for detection of gene doping must be specific to and will vary depending on the type of gene therapy. The purpose of this paper is to present the results of a systematic review of gene editing, gene therapy, and detection of gene doping in horses.Based on the published literature, gene therapy has been administered to horses in a large number of experimental studies and a smaller number of clinical cases. Detection of gene therapy is possible using a combination of PCR and sequencing technologies. This summary can provide a basis for discussion of appropriate and inappropriate uses for gene therapy in horses by the veterinary community and guide expansion of methods to detect inappropriate uses by the regulatory community.

show abstract

Application of gene therapy in the treatment of superficial digital flexor tendon injury in horses

Cited by 10 publications

References 18 publications

The Role of Vascular Endothelial Growth Factor in Tendon Healing

The Role of Vascular Endothelial Growth Factor in Tendon Healing

Identification of processed pseudogenes in the genome of Thoroughbred horses: Possibility of gene‐doping detection considering the presence of pseudogenes

Administration and detection of gene therapy in horses: A systematic review

Contact Info

Product

Resources

About