A cure for the deadly human immunodeficiency virus (HIV) infection might well be much closer than the world thought earlier.
In a significant breakthrough, a group of scientists -- including an Indian -- seems to have discovered a way to remove the virus from infected cells, said a recent study.
The scientists engineered an enzyme -- called Tre -- that attacks the very DNA of the HIV virus and cuts it out of the infected cell, according to the study published in Science magazine.
The enzyme, wrote lead author of the paper Indrani Sarkar, 'would need efficient and safe means of delivery and would have to be able to function without adverse side effects.'
Sarkar participated in this project while she was at the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden. Currently, she is the associate scientific manager, Syngene International Ltd, Biocon Park.
The study says that the Tre enzyme is still in experimental stages and not yet ready to be used as a treatment, but hints at a very strong possibility that this might offer a cure to the more than 40 million HIV-infected people on the planet.
HIV is a retrovirus: it infects the cells in the human body and also splices its own genetic code into the host cell's DNA, thereby merging itself with the patient's own tissues.
What led to this amazing discovery? What was the motivation? Will this pave the way for more such discoveries?
We sought answers to these, and other, queries from Indrani Sarkar, who squeezed out time from her busy schedule to answer them through e-mail. Excerpts:
Your discovery is being lauded worldwide as the potential cure for the HIV infection. How long did it take you to zero in on the enzyme -- Tre-- which attacks the DNA of the HIV virus and cuts it out of the infected cell?
The entire thing was essentially my PhD project, involving directed evolution of Tre and analysing its application in anti-HIV/retroviral therapy.
The project, including the final experiments on HIV infected cells, took more than four years.
The novelty of the work lies in the fact that for the first time the HIV provirus has been directly targetted and shown to be recombined out from genome of infected cells, showing that there is a way of evicting the virus from the genome.
This basically opens up a new way to throw out the virus, and the 'proof of principle' study is applicable to any retroviral infection. The most important aspect is that this shows a way to eradicate the virus and not just suppress the virus.
The first challenging task, of course, was to make Tre, using directed evolution. It took us a year-and-a-half, followed by screening and selection of the final recombinase. This was again a lengthy process, which was followed by more challenging experiments before reaching the virus-infected cells.
Finally, our efforts bore fruit.
Please tell us how did you arrive at the conclusion that HIV can be removed from infected cells?
The project was meant to use site-specific recombination on an integrated HIV provirus to remove it from the genome by using an evolved recombinase. The idea was there from the beginning, but the experiments in HIV infected cells showed us that this principle actually succeeds in removing the virus.
What makes HIV so deadly, however, is its ability to insert itself into the body's cells and force those cells to produce new infection.
Is Tre recombinase, the enzyme you developed, safe to use on people? If not, when will it be?
The work we did was the first approach, the baby step as Dr Engelman from Harvard said in the perspective that appeared in the same issue of Science, which had an account of our work.
Loads of work is yet to be done to transform this procedure into a therapy. That by itself is a mega project and will require years. This is right now a 'proof of principle' that a Tre-like enzyme can be used to snip the integrated provirus from the genome.
When do you expect Tre recombinase to hit the market as an 'effective antidote to HIV'?
It's too early to say anything now.
Could you tell us briefly about yourself and your colleagues who worked on this project?
I am from Kolkata. After finishing college in that city, I went to the Indian Institute of Technology, Kharagpur, for M.Tech in 2000-2002. Thereafter, I went to Germany to pursue PhD in the Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, in the group of Frank Buchholz. The latter was my PhD supervisor.
During the course of this project, we collaborated with Prof Joachim Hauber and Dr Ilona Hauber, eminent HIV virologists, from Heinrich Petter Institute of Virology, Hamburg, for final experiments with HIV infected cells. It was a wonderful collaboration and I am grateful to my supervisors and collaborators.
HIV treatment in India is still quite expensive. With mobile and migrant population like truck drivers, sex workers and migrant labourers being the usual victims, how affordable will Tre recombinase be for end users?
All these questions cannot be answered at this point.
Does Tre recombinase pave the way for more interesting discoveries to counter HIV/AIDS? If so, how?
Definitely this discovery will invite new ideas from HIV scientists and directed evolution scientists all over the world. Hopefully, it will bring in open up new avenues to combat this deadly virus.
