How do cell and gene therapy differ?

Cell and gene therapy share the same therapeutic goals - the prevention, treatment and, ultimately, the cure of diseases. However, cell and gene therapy are different approaches with unique mechanisms and characteristics. While cell therapy involves the transfer of cells with relevant, patient-specific functions, which have been cultivated ex vivo, gene therapy works by replacing, inactivating or introducing genetic material into the targeted cells. Cell and gene therapy are complementary techniques that are often used together in the treatment of many diseases. Together, cell and gene therapy provide feasible therapeutic options for diseases with few or no effective traditional treatments, brightening the future of therapeutics.

Basic mechanisms of gene and cell-based therapy

Cell and gene therapy are both concerned with the treatment of diseases using a patient’s genetic material; cell therapies introduce cells with a particular function to aid in treatment, while gene therapy focuses on modifying genetic material. In gene-based therapy, specific genetic material can be administered to the patient in a vector that transfers the genetic material into the target cell. Modified natural viruses, usually either retroviruses or adeno-associated viruses, and plasmids are the most efficient vectors for DNA/RNA transfer into a cell. These viruses undergo genetic modification to remove the disease-causing genes and replace them with the functioning gene/genes, along with sequences that control its expression, whilst keeping the viral coat/envelope intact for effective transfer to the cell. Plasmids that have been modified with the addition of an artificial membrane are also useful vectors in gene-based therapy. Viral and plasmid vectors allow only for the addition of genes to patient target cells.¹

Recent genome editing techniques, however, are pushing gene therapy to new heights, allowing for gene addition, ablation and ‘correction’. The landscape of genome editing was drastically improved in 2012 thanks to the discovery of the relatively simple and inexpensive gene-editing technique CRISPR-Cas9. This revolutionary technique can efficiently cleave a DNA site of interest through the straightforward design of a sequence-specific guide RNA which complements the target site of interest. This impeccably precise genome editing tool is helping scientists to overcome issues associated with semi-random gene addition from viral and plasmid vectors.²

As noted above, it is here where cell and gene therapy differ, as cell-based therapy involves the injection of whole cells, manipulated and created from patient or donor stem cells. Stem cells are self-renewable cells that can give rise to different cell lineages/types, a highly attractive feature which makes stem cell research the focus of cell-based therapy. The three main stem cell groups used in cell therapy are embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult stem cells such as mesenchymal stem cells (MSCs). With ESCs and iPSCs being limited in their clinical applications due to ethical and practical reasoning, MSCs are the focus of cell therapy for regenerative medicine and are now regularly used in clinical trials.³

Applications of cell and gene-based therapy

Although the mechanisms of cell and gene therapy differ, cell and gene therapy greatly overlap and are used together to treat a vast variety of diseases. Cell and gene therapy are important in the treatment of Dystrophinopathies, caused by mutations in the Duchenne Muscular Dystrophy (DMD) gene. Cell and gene therapy work together by replacing damaged cells with healthy, functioning cells and replacing and/or repairing the mutated DMD gene.⁴ This is one of many examples where combining cell and gene therapy results in more effective treatment. Cell and gene therapy are also even improving regenerative treatments in patients with spinal fusion.⁵

Cell and gene therapies have also opened new avenues for treating diseases that have been persistently difficult to combat. Oncology has benefited greatly from the application of these novel approaches, particularly when it comes to treating cancers with very poor clinical outcomes, such as pancreatic cancer.⁶

So, although different in their mechanisms and characteristics, cell and gene therapy are united in their aims and applications in therapeutics. Thanks to broad technological advances, cell and gene therapy are quickly becoming two of the most promising tools for treating extremely devastating diseases.

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References

1. Sinclair, A., Islam, S. and Jones, S. (2016). Gene Therapy: An Overview of Approved and Pipeline Technologies. [online] PubMed. Available at: https://pubmed.ncbi.nlm.nih.gov/30855777/ [Accessed 21 Aug. 2023].
2. Dunbar, C.E., High, K.A., Joung, J.K., Kohn, D.B., Ozawa, K. and Sadelain, M. (2018). Gene therapy comes of age. Science, [online] 359(6372), p.eaan4672. doi:https://doi.org/10.1126/science.aan4672.
3. Jovic, D., Yu, Y., Wang, D., Wang, K., Li, H., Xu, F., Liu, C., Liu, J. and Luo, Y. (2022). A Brief Overview of Global Trends in MSC-Based Cell Therapy. Stem Cell Reviews and Reports, 18(5), pp.1525–1545. doi:https://doi.org/10.1007/s12015-022-10369-1.
4. Barthélémy, F. and Wein, N. (2018). Personalized gene and cell therapy for Duchenne Muscular Dystrophy. Neuromuscular Disorders, 28(10), pp.803–824. doi:https://doi.org/10.1016/j.nmd.2018.06.009.
5. Barba, M., Cicione, C., Bernardini, C., Campana, V., Pagano, E., Michetti, F., Logroscino, G. and Lattanzi, W. (2014). Spinal Fusion in the Next Generation: Gene and Cell Therapy Approaches. The Scientific World Journal, 2014, pp.1–9. doi:https://doi.org/10.1155/2014/406159.
6. Singh, H.M., Ungerechts, G. and Tsimberidou, A.M. (2015). Gene and cell therapy for pancreatic cancer. Expert Opinion on Biological Therapy, 15(4), pp.505–516. doi:https://doi.org/10.1517/14712598.2015.1001734.