Epigenetic and Gene Modification Precision Medicine Approaches for the “Chronic Destructive Perio-Diseases”: Periodontitis and Peri-implantitis
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The mainstay of periodontal and peri-implantitis treatment is the mechanical and chemical eradication of the plaque biofilm both professional and as a preventive home care regime. Precision medicine approaches are highly applicable to these common chronic inflammatory diseases that feature a strong genetic and individual susceptibility profile that has the possibility to be modified. In order to improve periodontal health and create resistance to new disease, individual susceptibility elements need to be identified and genetically and molecularly modified. This review seeks to take our thinking further and utilize current accepted paradigms regarding the etiology of the disease, the contributing host factors and using precision medicine-like approaches using our vast laboratory and animal-based knowledge of systems biology, molecular, and –omics knowledge, to fashion new approaches. One approach is the reduction in inflammation by utilizing CRISPR to replace genetic haplotypes responsible for defective IL-8 response. Another approach considered is modifying the epigenome, specifically reducing the methylation of TLR2 related DNA to improve the receptor function in the innate immune response to the biofilm. And lastly we will review CRISPR modification of NOD receptor genes to improve PMN-related netosis to improve host response to the biofilm. Currently, gene modification, deletion, and replacement therapies, predominantly through CRISPR, are starting to become FDA-approved and may develop relevance for oral diseases. Thus, we will review these examples of precision medicine approaches to reducing periodontal susceptibility that might prove in future to have therapeutic utility or provide inspiration to develop other approaches to exploit the enormous body of molecular and genetic knowledge on the etiology of the disease to address this common and debilitating disease.
KeywordsCRISPR Epigenetics NOD receptors Periodontitis Peri-implantitis Gene modification Netosis IL-8 Haplotypes
Dr. Manjunathata Benakanakere collaborated on all of the work presented in this review and I am grateful to him for his inspirational intellect and support.
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