Mice aid development of new weapon against HIV

For the past 25 years scientists have sought to develop treatments for HIV, the virus which causes AIDS.  They have had notable successes in that time, particularly with the development of highly active antiretroviral therapy (HAART) which combines several drugs in a potent antiviral cocktail.  Unfortunately HAART does not cure HIV infection, and in many  patients HIV eventually evolves resistance to the drugs. Scientists are therefor constantly working on developing new treatments that can stop HIV progressing to AIDS, and ultimately aim to identify treatments that can eliminate HIV infection altogether.

In the past few years some scientists have explored the potential of small interfering RNAs (siRNAs) in combatting HIV.  The siRNAs work by preventing a virus gene from producing its protein product, thereby preventing the gene from doing its job, and studies done using human cells in petri dishes have shown that siRNAs can block HIV infection.  The problem is that scientists needed a way to target the siRNAs to the T-cells of the immune system which are infected with HIV.
In a paper published online in Cell this week (1) Dr. Premlata Shankar and colleagues describe how they developed a way of targeting the siRNA to the T-cells by using a modified antibody specific for a protein expressed on the surface of those T-cells.  Scientific American discuss this work, while a more detailed discussion can be found at here.

A key part of Dr. Shankar’s work was the development and use of a mouse model of HIV to assess whether the correct cells in the body were being targeted by the modified antibodies.  Mice don’t normally become infected with HIV, but by genetically modifying mice so that own immune system do not develop and then transplanting human umbilical cord stem cells into the mice they were able to produce mice with “humanized” immune systems.  These mice can be infected by HIV and eventually develop an AIDS like illness.  Dr. Shankar’s team found that they could deliver the siRNA’s to the T-cells specifically and block HIV infection the depletion of T-cells that is a hallmark of HIV infection, all without causing any harm to the cells of the immune system.

It is important to note that this is not a cure, several types of cell apart from T-cells are infected by HIV so antibodies that target those other cells will also need to be developed and evaluated.  Still this is excellent news and if further testing indicates that it is safe it may well translate into a treatment for human HIV patients that can be used along side HAART.

Cheers
Paul

1)  Kumar P. et al. “T Cell-Specific siRNA Delivery Suppresses HIV-1 Infection in Humanized Mice” Cell Online 2008 DOI: 10.1016/j.cell.2008.06.034

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