Post 4: Applying genetic modification and the D. radiodurans bacteria to MS

Our group is taking multiple approaches to cure multiple sclerosis including the genetic approach, interface approach, and applied cancer research approach to provide multiple paths of intervention and prevention of the symptoms and development of MS in all of its stages. Each person in our group is separately researching one of these topics in order to “fight” multiple sclerosis in different ways. I am focusing on curing multiple sclerosis on the genetic level using the Deinococcus radiodurans bacterium as a model for cell self-reparation. The D. radiodurans bacteria can withstand high amounts of radiation, destroying both its cellular components and its genome, and can fully self repair itself afterwards using extended synthesis-dependent strand annealing (ESDSA) which includes DNA polymerase I (Pol I)-dependent DNA synthesis and RecA-dependent recombination processes (Slade, 2009). These self repairing functions of the D. radiodurans bacterium is encoded in its genome specifically on chromosome II (2009). By studying what genes on the D. radiodurans’ chromosome II lead to the expression of self-reparation and using current gene editing methods such as CRISPR, it may be possible to genetically modify the human genome to promote remyelination and neuron self-reparation for cells affected by MS.

Current treatment of multiple sclerosis today includes gene therapy, modification of microglia, and t-cell therapy, all of which prove partially beneficial to treating MS but cannot fully cure it nor fully reverse the damage to cells caused by the disease. By using gene modification to edit the human genome to contain sequences that code for self-reparation of neurons and oligodendrocyte cells surrounding the peripheral and central nervous system based off of the genes on chromosome II of the D. radiodurans bacteria that code for self-reparation, full cell reparation would inhibit the progression of MS. Remyelination rates decrease as MS progresses (Podbielska, 2013). Therefore having genes that promote self-reparation would increase rates of remyelination, rebuilding the myelin sheath, and lessening the symptoms of cognitive and physical impairments associated with MS. MS could be cured without knowing the full set of genes and gene markers that cause the disease using CRISPR to edit the human genome to contain genes that promote cell reparation modeled after the ESDSA process that D. radiodurans use. Even when the immune system would cause the destruction of the myelin sheath and destruction of oligodendrocyte cells, the edited human genome would contain instructions to self-repair these cells and neurons. One gap that creates difficulties for this approach is that several of the processes that the D. radiodurans bacterium uses to repair its genome are still unknown and not fully understood. Another challenge includes that the ESDSA process of genomic reparation would need modification for application in the use of reparation for other cellular components such as the myelin sheath of the neurons. A problem that results from using CRISPR is the limited current knowledge of how using the genome of a bacteria as a model for self-repairing genes could be directly applied to editing specific genes on the human genome. Even with these challenges, gene modification to promote self-reparation of cells destroyed by MS using the D. radiodurans bacteria’s genome self-reparation as a model could lead to a direct cure of the disease and several other autoimmune diseases.

Podbielska, M., Banik, N. L., Kurowska, E., & Hogan, E. L. (2013). Myelin Recovery in Multiple Sclerosis: The Challenge of Remyelination. Brain Sciences, 3(3), 1282–1324. http://doi.org/10.3390/brainsci3031282

Slade, D., Lindner, A. B., Paul, G., & Radman, M. (2009, March 19). Recombination and Replication in DNA Repair of Heavily Irradiated Deinococcus radiodurans. Retrieved September 28, 2018, from https://www.sciencedirect.com/science/article/pii/S009286740900066X

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