Hyderabad: Scientists at the city-based Centre for Cellular
and Molecular Biology have found genome regulatory elements that can
help in effective and successful introduction of genes from external
sources into an organism. These regulatory elements are conserved
during evolution and form part of the mechanism involving gene therapy
and making transgenic animals and plants.
Gene therapy, which is likely to emerge as a major frontier of medical
science in near future, has its drawbacks too. But the findings of the
CCMB team headed by Dr Rakesh K Mishra may help in overcoming these
drawbacks to make gene therapy really reliable in treating genetic
diseases, for which there's no cure at present. There are a number of
diseases for which gene therapy is the only hope.
In gene therapy, defective genes are corrected by introducing
functional genes in the patient body. In many cases though the gene
therapy solves the identified problem, it leads to emergence of new
health issues. Some times this is because the genomic context in which
new gene is inserted leads to inappropriate interactions of the
genetic material in the vicinity.
The CCMB team has noticed that there exists "boundary elements", which
divide the genomic information into different compartments so as to
avoid unwanted disturbance or cross-talk.
Thanks to these boundary elements, even if a new gene is inserted to
replace a defective gene, the genetic information in the region does
not get troubled. This mechanism works across the species in plants
and animals, ranging from the simple Drosophila to the complex human
"Our finding has significant advantage to gene therapy and development
of transgenic plants and animals. In gene therapy it will protect the
gene which we insert from being mis-regulated. It will also help in
making transgenic plants and animals more regulated by reducing
undesired features, which crop up due to accidental misregulation.
Whatever you want to make will be more effective and less disturbed,"
said Dr Rakesh Mishra.
Dr Mishra's team followed "Hox genes" that determine which part of the
fertilised egg mass to develop into which body part. They help in
providing proper shape to the body, whether insect or mammal,
including formation of the organs and positioning them in order.
"In vertebrates, distinctly expressed Hox genes are closely spaced.
This raises the possibility of boundary elements being present in the
intergenic locations to mark the regulatory features of each gene, in
a manner similar to Drosophila homeotic gene regulation. The
Evx2-Hoxd13 region in the mouse HoxD complex is one such example where
two differentially expressed genes are separated by about 9 kb of
intervening DNA, he added. These findings have been published in the
prestigious international journal ‘Development’ recently.
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