Review on gene therapy and its application in veterinary medicine
Gene therapy in veterinary medicine
DOI:
https://doi.org/10.62310/liab.v5i2.220Keywords:
Gene Therapy, Non-viral Vector, Monogenic Disease, Veterinary Medicine, Viral VectorsAbstract
The discovery of gene therapy is a pillar of contemporary science and has turned into a revolution in medical treatment. While there are some limitations associated with this approach, its advantages continue to grow. Gene therapy is a therapeutic approach that involves transferring DNA into an individual to correct defective genes and treat conditions not responding to conventional medication. Over time, the scope of gene therapy has expanded from a primary focus on treating monogenetic disorders to a more complex approach that includes induction of cell death in disease management. However, efficient delivery of enough genetic material to target cells or tissues and maintaining gene expression for the desired duration are the challenges in gene therapy. There are numerous ways to transfer genetic material to specific cells or tissues. They can be broadly categorized into viral and non-viral techniques. Among viral vectors adenovirus (AV), adeno-associated virus (AAV), herpes simplex virus (HSV), lentivirus (LV), and poxvirus have been extensively studied. Non-viral delivery methods include extracellular vesicles, bacteria, nanoparticles, and direct injection of naked DNA. Advancements in genetic engineering have enabled the development of species-specific gene therapies for animals, while reducing risks of unintended consequences and adverse effects. In addition, of providing new and modern choices of treating a variety of animal ailments, gene therapy can potentially address the issues such as pet overpopulation. Numerous animal health issues, including hemophilia, cardiovascular disorders, diabetes, muscular dystrophy, lysosomal storage disorders, eye problems, cancer, and infectious diseases have recently been treated by gene therapy. Though considerable success have been achieved in human medicine, gene therapy still remains underutilized in veterinary medicine. Therefore, broader application across different species and targeted veterinary research is essential to fully realize its potential in animal health care.
Metrics
References
Acland GM, Aguirre GD, Bennett J, Aleman TS, Cideciyan AV, Bennicelli J, Dejneka NS, Pearce-Kelling SE, Maguire AM, Palczewski K, Hauswirth WW. Jacobson SG. (2005). Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness. Molecular Therapy 12(6): 1072-1082. https://doi.org/10.1016/j.ymthe.2005.08.008
Aiuti A, Bacchetta R, Seger R, Villa A, Cavazzana-Calvo M. (2012). Gene therapy for primary immunodeficiencies. Current Opinion in Immunology 24: 585-591. https://doi.org/10.1016/j.coi.2012.07.012
Alnasser SM. (2021). Review on mechanistic strategy of gene therapy in the treatment of disease. Gene 769: 145246. https://doi.org/10.1016/j.gene.2020.145246
Amoasii L, Hildyard JC, Li H, Sanchez-Ortiz E, Mireault A, Caballero D, Harron R, Stathopoulou TR, Massey C, Shelton JM, Bassel-Duby R. (2018). Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy. Science 362(6410): 86-91. https://doi.org/10.1126/science.aau1549
Argyle DJ. (1999). Gene therapy in veterinary medicine. Veterinary Record 144: 369-376. https://doi.org/10.1136/vr.144.14.369
Athanasopoulos T, Munye MM, Yáñez-Muñoz RJ. (2017). Nonintegrating gene therapy vectors. Hematology/Oncology Clinics of North America 31(5): 753-770. https://doi.org/10.1016/j.hoc.2017.06.007
Batty P, Lillicrap D. (2019). Advances and challenges for hemophilia gene therapy. Human Molecular Genetics 28(R1): R95-R101. https://doi.org/10.1093/hmg/ddz157
Bradbury AM, Gurda BL, Casal ML, Ponder KP, Vite CH, Haskins ME. (2015). A review of gene therapy in canine and feline models of lysosomal storage disorders. Human Gene Therapy Clinical Development 26(1): 27-37. https://doi.org/10.1089/humc.2015.002
Cantore A, Ranzani M, Bartholomae CC, Volpin M, Valle PD, Sanvito F, Sergi LS, Gallina P, Benedicenti F, Bellinger D, Raymer R. (2015). Liver-directed lentiviral gene therapy in a dog model of hemophilia B. Science Translational Medicine 7(280): 277ra28. https://doi.org/10.1126/scitranslmed.3010274
Chamberlain JS. (2002). Gene therapy of muscular dystrophy. Human Molecular Genetics 11(20): 2355-2362. https://doi.org/10.1093/hmg/11.20.2355
Coughlan L, Alba R, Parker AL, Bradshaw AC, McNeish IA, Nicklin SA, Baker AH. (2010). Tropism-modification strategies for targeted gene delivery using adenoviral vectors. Viruses 2(10): 2290-2355. https://doi.org/10.3390/v2102290
Doudna JA. (2020). The promise and challenge of therapeutic genome editing. Nature 578(7794): 229-236. https://doi.org/10.1038/s41586-020-1978-5
Dunbar CE, High KA, Joung JK, Kohn DB, Ozawa K, Sadelain M. (2018). Gene therapy comes of age. Science 359(6372): 4672. https://doi.org/10.1126/science.aan4672
Emery AE. (2002). The muscular dystrophies. Lancet 359: 687–695. https://doi.org/10.1016/S0140-6736(02)07815-7
Ginn SL, Curtin JA, Smyth CM, Latham M, Cunningham SC, Zheng M, Hobson L, Rowe PB, Alexander IE, Kramer B, Wong M. (2005). Treatment of an infant with X‐linked severe combined immunodeficiency (SCID‐X1) by gene therapy in Australia. Medical Journal of Australia 182(9): 458-463. https://doi.org/10.5694/j.1326-5377.2005.tb06785.x
Hama S, Akita H, Ito R, Mizuguchi H, Hayakawa T, Harashima H. (2006). Quantitative comparison of intracellular trafficking and nuclear transcription between adenoviral and lipoplex systems. Molecular Therapy 13(4): 786-794. https://doi.org/10.1016/j.ymthe.2005.10.007
Hashimoto T, Gibbs D, Lillo C, Azarian SM, Legacki E, Zhang XM, Williams DS. (2007). Lentiviral gene replacement therapy of retinas in a mouse model for Usher syndrome type 1B. Gene Therapy 14(7): 584-594. https://doi.org/10.1038/sj.gt.3302897
Heeley AM, O’Neill DG, Davison LJ, Church DB, Corless EK, Brodbelt DC. (2020). Diabetes mellitus in dogs attending UK primary-care practices: frequency, risk factors and survival. Canine Medicine and Genetics 7: 1-19. https://doi.org/10.1186/s40575-020-00087-7
High KA, Roncarolo MG. (2019). Gene Therapy. New England Journal of Medicine 381 (5): 455–464. https://doi.org/10.1056/NEJMra1706910
Huang Y, Liu X, Dong L, Liu Z, He X, Liu W. (2011). Development of viral vectors for gene therapy for chronic pain. Pain Research and Treatment 2011: 968218. https://doi.org/10.1155/2011/968218
Hurlbut GD, Ziegler RJ, Nietupski JB, Foley JW, Woodworth LA, Meyers E, Scheule RK. (2010). Preexisting immunity and low expression in primates highlight translational challenges for liver-directed AAV8-mediated gene therapy. Molecular Therapy 18(11): 1983-1994. https://doi.org/10.1038/mt.2010.175
Jaén ML, Vilà L, Elias I, Jimenez V, Rodó J, Maggioni L, Ruiz-de Gopegui R, Garcia M, Muñoz S, Callejas D, Ayuso E. (2017). Long-term efficacy and safety of insulin and glucokinase gene therapy for diabetes: 8-year follow-up in dogs. Molecular Therapy Methods & Clinical Development 6: 1-7. https://doi.org/10.1016/j.omtm.2017.03.008
Jafarlou M, Baradaran B, Saedi TA, Jafarlou V, Shanehbandi D, Maralani M, Othman F. (2016). An overview of the history, applications, advantages, disadvantages and prospects of gene therapy. Journal of Biological Regulators and Homeostatic Agents 30(2): 315-321.
Komáromy AM, Bras D, Esson DW, Fellman RL, Grozdanic SD, Kagemann L, Miller PE, Moroi SE, Plummer CE, Sapienza JS, Story ES. (2019). The future of canine glaucoma therapy. Veterinary Ophthalmology 22(5): 726-740. https://doi.org/10.1111/vop.12678
Litvin YA, Zakirova EY, Zhuravleva MN, Rizvanov AA. (2016): Generation of plasmid DNA expressing species-specific horse VEGF164 and FGF2 factors for gene therapy. BioNanoScience 6: 550-553. https://doi.org/10.1007/s12668-016-0273-2
Lowenthal JW, York JJ, O'Neil TE, Steven RA, Strom DG, Digby MR. (2006). Potential use of cytokine therapy in poultry. Veterinary Immunology and Immunopathology 63(1-2): 191-198. https://doi.org/10.1016/S0165-2427(98)00212-5
Mangraviti A, Tzeng SY, Kozielski KL, Wang Y, Jin Y, Gullotti D, Green JJ. (2015). Polymeric nanoparticles for nonviral gene therapy extend brain tumor survival in vivo. ACS Nano 9(2): 1236-1249. https://doi.org/10.1021/nn504905q
McCain J. (2005). The future of gene therapy. Biotechnology healthcare 2(3): 52. https://pubmed.ncbi.nlm.nih.gov/23393464/
Mintzer MA, Simanek EE. (2009). Nonviral vectors for gene delivery. Chemical Reviews 109(2): 259-302. https://doi.org/10.1021/cr800409e
Mohan RR, Martin LM, Sinha NR. (2021). Novel insights into gene therapy in the cornea. Experimental Eye Research 202: 108361. https://doi.org/10.1016/j.exer.2020.108361
Naldini L. (2011). Ex vivo gene transfer and correction for cell-based therapies. Nature Reviews Genetics 12(5): 301-315. https://doi.org/10.1038/nrg2985
Naso MF, Tomkowicz B, Perry WL, Strohl WR. (2017). Adeno-associated virus (AAV) as a vector for gene therapy. BioDrugs 31(4): 317-334. https://doi.org/10.1007/s40259-017-0234-5
Navarro SA, Carrillo E, Griñán-Lisón C, Martín A, Perán M, Marchal JA, Boulaiz H. (2016). Cancer suicide gene therapy: a patent review. Expert Opinion on Therapeutic Patents 26(9): 1095-1104. https://doi.org/10.1080/13543776.2016.1211640
Palffy R, Gardlik R, Hodosy J, Behuliak M, Reško P, Radvánský J, Celec P. (2009). Bacteria in gene therapy: bactofection versus alternative gene therapy. Gene Therapy 13(2): 101-105. https://doi.org/10.1038/sj.gt.3302635
Parayath NN, Parikh A, Amiji MM. (2018). Repolarization of tumor-associated macrophages in a genetically engineered non-small cell lung cancer model by intraperitoneal administration of hyaluronic acid-based nanoparticles encapsulating microRNA-125b. Nano Letters 18(6): 3571-3579. https://doi.org/10.1021/acs.nanolett.8b00689
Parker DG, Coster DJ, Brereton HM. (2010). Lentivirus-mediated gene transfer of interleukin 10 to the ovine and human cornea. Clinical Experiment Ophthalmology; 38: 405-13. https://doi.org/10.1111/j.1442-9071.2010.02261.x
Ramsey JP, Khatwani SL, Lin M, Boregowda R, Surosky R, Ramelmeier RA. (2021). Overview of analytics needed to support a robust gene therapy manufacturing process. Current Opinion in Biomedical Engineering 20: 100339. https://doi.org/10.1016/j.cobme.2021.100339
Shimotohno K, Temin HM.(1982). Loss of intervening sequences in genomic mouse α-globin DNA inserted in an infectious retrovirus vector. Nature 299: 265–268. https://doi.org/10.1038/299265a0
Sleeper MM. (2017). Status of therapeutic gene transfer to treat cardiovascular disease in dogs and cats. Veterinary Clinics of North America: Small Animal Practice 47(5): 1113-1121. https://doi.org/10.1016/j.cvsm.2017.04.005
Smith RH. (2008). Adeno-associated virus integration: virus versus vector. Gene Therapy 15(11): 817-822. https://doi.org/10.1038/gt.2008.55
Sorrentino BP. (2020). Gene therapy to protect hematopoietic cells from cytotoxic cancer drugs. Nature Reviews Cancer 2(6): 431-441. https://doi.org/10.1038/nrc823
Stonebraker JS, Bolton‐Maggs PH, Michael Soucie J, Walker I, Brooker M. (2010). A study of variations in the reported hemophilia A prevalence around the world. Hemophilia 16(1): 20-32. https://doi.org/10.1111/j.13652516.2009.02127.x
Sung YK, Kim SW. (2018). The practical application of gene vectors in cancer therapy. Integrative Cancer Science and Therapeutics 5: 1-5. https://doi.org/10.15761/ICST.1000287
Wang D, Tai PW, Gao G. (2019). Adeno-associated virus vector as a platform for gene therapy delivery. Nature Reviews Drug Discovery 18(5): 358-378. https://doi.org/10.1038/s41573-019-0012-9
Wasala NB, Hakim CH, Chen SJ, Yang NN, Duan D. (2019). Questions answered and unanswered by the first CRISPR editing study in a canine model of Duchenne muscular dystrophy. Human Gene Therapy 30(5): 535-543. https://doi.org/10.1089/hum.2018.243
Wolde SMW, Toth K. (2013). Adenovirus vectors for gene therapy, vaccination and cancer gene therapy. Current Gene Therapy 13(6): 421-433. https://doi.org/10.2174/1566523213666131125095046
Yla-Herttuala S, Raty JK, Lesch HP, Wirth T. (2008). Improving safety of gene therapy. Current Drug Safety 3(1): 46-53. https://doi.org/10.2174/157488608783333925
Yoon S, Fleeman LM, Wilson BJ, Mansfield CS, McGreevy P. (2020). Epidemiological study of dogs with diabetes mellitus attending primary care veterinary clinics in Australia. Veterinary Record 187(3): e22-e22. https://doi.org/10.1136/vr.105467
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Timotiwos Wogaso

This work is licensed under a Creative Commons Attribution 4.0 International License.
Accepted 2025-08-05
Published 2025-08-09