Byline: Sruthima. Gottumukkala, C. Dwarakanath, Sabitha. Sudarsan
Despite major advances in periodontal regeneration over the past three decades, complete regeneration of the lost periodontium on a regular and predictable basis in humans has still remained elusive. The identification of stem cells in the periodontal ligament together with the growing concept of tissue engineering has opened new vistas in periodontal regenerative medicine. In this regard, ribonucleic acid interference (RNAi) opens a new gate way for a novel RNA based approach in periodontal management. This paper aims to summarize the current opinion on the mechanisms underlying RNAi, in vitro and in vivo existing applications in the dental research, which could lead to their future use in periodontal regeneration.
Periodontitis is an inflammatory disease that causes pathological alterations in the tooth-supporting tissues, potentially leading to loss of periodontal structure and eventually tooth loss. The treatment of periodontal disease points to the need for more effective and efficient management of this condition, in an attempt to restrict its impact on general health and patient quality-of-life for which a wide range of treatment strategies have been in use with variable success to repair or regenerate the periodontal tissues to reduce the likelihood of tooth loss. Current efforts to reproduce a natural periodontium are based on the principles of tissue engineering.
Tissue engineering is a term that describes the application or use of cells, scaffolds and growth factors to restore, maintain or enhance tissue function. Various therapeutic approaches have been proposed in the recent times to enhance the regenerative potential of the periodontium in addition to the conventional procedures which include (i) conductive therapeutics, (ii) inductive therapeutics, (iii) cell based approach, (iv) protein based approach and (v) gene based approach. However, ribonucleic acid (RNA) based approach is a novel therapeutic modality, which provides a therapeutic platform for regeneration of the lost periodontium as well as inhibition of disease progression. RNA interference (RNAi) is an efficient natural mechanism for controlling gene expression based on gene silencing. In recent years, RNAi has become one of the most powerful tools for probing gene functions and rationalizing the drug design. It has been used as a potential therapeutic agent for a wide range of disorders, including cancer, infectious diseases, systemic and metabolic disorders.
Discovery of RNAi
A large number of small RNA molecules work in conjunction with proteins in ribonucleoprotein (RNP) complexes, which help in gene expression. These various RNP particles are now being extensively studied in an attempt to understand their specific roles in the gene expression and protein synthesis. In the early 1980s, investigators revealed that small RNA molecules (about 100 nucleotides (nt) in length) can bind to a complementary sequence in messenger RNA (mRNA) and inhibit translation in Escherichia coli . [sup], Until date, about approximately 25 cases of regulatory trans-acting antisense RNAs are discovered in E. Coli . [sup] However, this regulation of translation by antisense RNA's is also found in eukaryotes as was first demonstrated in 1993. It was found in a few experiments...