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Tuesday, Jul 03, 2007
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Indrani: new enzyme is like molecular scissors

Divya Gandhi

Indrani Sarkar

BANGALORE: “Think of it as molecular scissors,” explains Indrani Sarkar about an enzyme that she and a team of scientists recently constructed — a research outcome that has generated considerable interest in the scientific (and media) world.

It has been less than a year since she completed her Ph.D. on anti-retroviral therapy and just four days since her paper — co-authored with a team of scientists from the Max Plank Institute of Molecular Cell Biology and Genetics, Dresden, and the University of Hamburg’s Heinrich Pette Institute for Experimental Virology and Immunology — was published in the reputed Science magazine. But she is already accustomed to having to communicate the significance of this re search on the human immunodeficiency virus (HIV) in simple language for the media.

The new enzyme has the capacity to “recognise and cut the virus out of the genome of the infected cell,” Dr. Sarkar says. With a deft sketch, she starts at the beginning, demonstrating how the retrovirus HIV integrates itself into the human genome.

“The biggest challenge with treating HIV is that the virus goes into a dormant, asymptomatic phase. The present-day treatment, which targets proteins produced when the virus is actively dividing, becomes ineffective at this stage. The virus also mutates and often develops resistance to current-day treatment regimes,” she says.

There is a need to target these reservoirs of latent viruses.

“And the only way to cure HIV is to get rid of the virus completely,” she says. Tre, the enzyme that Dr. Sarkar and her team constructed after a year and 126 “cycles of mutation,” completely depleted HIV in the human genome in three months in laboratory conditions.

The principle of the new process is that Tre targets the genome of the virus itself, evicting it from the human cell. “This is a very exciting, novel approach. But it is far too early to say when this will go into therapy. This only shows the principle on how it works,” she explains.

On how close this research is to clinical trials, Dr. Sarkar says, “it will take a minimum of 10 years before clinical trials can even be contemplated,” firmly dispelling illusions of an imminent cure for HIV/AIDS.

“The most important word here is ‘delivery.’ The biggest challenge, as with any other drug being developed, is to make sure that the enzyme reaches the sequences that we intend it to reach. Delivery will be a different project all by itself. We will have to ensure there are no side effects, that only sequences that we intend to remove are removed,” she said.

Although these results “represent perhaps only a baby step” towards a possible cure, Tre “proves that enzymatic removal of integrated HIV-1 from human chromosomes is a current-day reality,” writes Alan Engelman of the Department of Cancer, Immunology and AIDS at Harvard University, in a perspective paper in Science.

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