Impact of gene therapy on dentistry

• Pain : Managing or eliminating pain is a major part of dental practice. The use of gene transfer technology offers a potentially novel approach to manipulate specific localized biochemical pathways involved in pain generation. It may be particularly useful for managing chronic and intractable pain. Viral mediated transfer of genes encoding opiate peptide to peripheral and central neurons can lead to antinocioceptive effects.
  
  
• DNA vaccinations : Classical vaccination against dental caries and periodontal disease is now being replaced by directly delivering DNA in a plasmid. In 1999 extensive research was carried out using plasmid DNA encoding the porphyomonas gingivalis fimbrical gene. This gene led to production of fimbrial protein locally in salivary gland tissue of mice. With consequent production of slgA the immunoglobulin could neutralize P.gingivalis and limit its ability in plaque formation. Furthermore any secreted fimbrial protein in saliva could bind to plaque and thereby inhibiting P.gingivalis to developing plaque.
  
  
• Gene transfer to keratinocytes : There are several features that make epidermal and oral mucosal keratinocytes attractive for treating local tissue disorders and as a systemic gene therapeutic. That is because
  
  
  • Monitoring is easy, because genetically modified tissue is accessible.
  • Preclinical assessment is accurate since culture models are established.
  • Expression of therapeutic genes can be achieved with the use of topically applied agents.
  • Transplantation of keratinocytes sheets is an established medical procedure.
  • Keratinocytes gene therapy is reversible because genetically modified tissue can be excised readily.
  
  
  
• Head and neck cancer : The general strategy is to express a gene product that will result in cancer cell death. In normal cells, the tumor suppressive protein p53 monitors the integrity of the genome and responds to any DNA damage by inducing cell cycle arrest, to allow repair, or apoptosis if repair is impossible. In head and neck cancers p53 tumor suppressor gene mutation is between 45-70%. This aspect has lead to development of recombinant adenovirus that selectively replicates and kills p53 -deficient cells. The adenovirus replicate in cells with mutated p53 protein but spares cells with normal p53 protein. The more recent studies have shown use of chemotherapy along with gene therapy and is highly successful in patient with recurrent and resistant tumor. Cis-platinum and 5-fluorouracil was used along with recombinant adenovirus therapy. Most future gene therapy-based cancer treatment will be combined with conventional Rx. Such augmentive approaches, rather the gene transfer alone probably will be used to reduce tumor burden and help maintain quality of life in patients with head and neck cancer and other solid tumors.