The Hyderabad based CCMB is currently targeting both DNA and RNA viruses to determine whether viral resistance in animals is related to post-transcriptional gene silencing (PTGS).
Gene silencing is important for cellular differentiation, viral resistance in plants, silencing of transposable element, sex specific regulation of sex determining genes, controlling hetero-chromation formation and cell division.
To understand the whole scenario of gene silencing mechanisms, CCMB's laboratory is focusing on identification of new candidate genes and characterization of their operation pathway. They are also in the process of determining the molecular relationship between Transcriptional Gene Silencing, PTGS and viral resistance in animal species, revealed Dr Utpal Bhadra, a senior scientist with CCMB.
His study found that post-transcriptional gene silencing (PTGS) exhibits molecular hallmarks typical of RNA interference (RNAi) including the production of small interfering 21-23 nucleotide double stranded RNA which act as homology for sequence-specific RNA degradation.
Advantages of RNAi is that they can silence any gene in any time point as a specific set of cells, they are highly specific, block viral infection and proliferation in animals and plants, knock down multiple genes in one step. There is lot of scope for RNAi in drug and vaccine discovery, gene therapy for infectious diseases and viral resistance. The technology gained lot of prominence since 2002.
Use of high throughput screening and powerful antisense technology is planned for a genome -wide survey of functional genomics as well as the identification of new targets for viral infection. In this process, DNA chips for baculovirus have been developed. The ultimate aim would be to determine the viral genes, which are related to infections. Projects targeting flavivirus, HPV and encephalitis are in progress.
Dr Bhadra's team is also working on narcolepsy (sleeping disorder) and neurological diseases. One out of 2000 humans is affected by narcolepsy, which appears to be related to feeding behaviour, biological rhythm, and symptoms of memory loss and Alzheimer.
RNA based drugs are currently in clinical trials. Asylum, San Francisco is working on hepatitis. Clinical trails are in progress and the drug is expected to hit the markets by 2005. Boston based Avocal is working on viral and cancer drugs, and the drugs are expected to be launched by 2005. Avocal is also investing $ 43 million on HIV drugs.
In Asia, there are various centres that are working on this technology. There are centres in Japan, Taiwan, China and a new centre is coming up in Pakistan with an investment of $10 million which is to work on vaccine development and drug targeting. Pakistan govt. is to arrange funds for this proposed centre that is to be set up in the Agha Khan Cencer Institute. India is yet to make serious efforts in this direction.
Dr Bhadra shared his research experiences at the 101st meeting of Medically Aware and Responsible Citizens of Hyderabad (MARCH).