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Vegas
06-28-2007, 04:01 PM
http://www.news.com.au/story/0,23599,21987906-23109,00.html

IN a breakthrough that could potentially lead to a cure for HIV infection, scientists have discovered a way to remove the virus from infected cells, a study released today said.

The scientists engineered an enzyme which attacks the DNA of the HIV virus and cuts it out of the infected cell, according to the study published in Science magazine.

The enzyme is still far from being ready to use as a treatment, the authors warned, but it offers a glimmer of hope for the more than 40 million people infected worldwide.

“A customised enzyme that effectively excises integrated HIV-1 from infected cells in vitro might one day help to eradicate (the) virus from AIDS patients,” Alan Engelman, of Harvard University's Dana-Farber Cancer Institute, wrote in an article accompanying the study.

Current treatments focus on suppressing the HIV virus in order to delay the onset of AIDS and dramatically extend the life of infected patients.

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.

“Consequently the virus becomes inextricably linked to the host, making it virtually impossible to 'cure' AIDS patients of their HIV-1 infection,” Mr Engelman explained.

That could change if the enzyme developed by a group of German scientists can be made safe to use on people.

That enzyme was able to eliminate the HIV virus from infected human cells in about three months in the laboratory.

The researchers engineered an enzyme called Tre which removes the virus from the genome of infected cells by recognising and then recombining the structure of the virus's DNA.

This ability to recognise HIV's DNA might one day help overcome one of the biggest obstacles to finding a cure: the ability of the HIV virus to avoid detection by reverting to a resting state within infected cells which then cease to produce the virus for months or even years.

“Numerous attempts have been made to activate these cells, with the hope that such strategies would sensitise the accompanying viruses to antiviral drugs, leading to virus eradication,” Mr Engelman wrote.

“Advances with such approaches in patients have been slow to materialise.”

New experiments must be designed to see if the Tre enzyme can be used to recognise these dormant infected cells, he wrote.

“Although favourable results would represent perhaps only a baby step toward eventual use in patients, the discovery of the Tre recombinase proves that enzymatic removal of integrated HIV-1 from human chromosomes is a current-day reality,” he said.

The researchers who developed the enzyme were optimistic about their ability to design additional enzymes which would target other parts of the virus's DNA.

However they warned that there were significant barriers to overcome before the enzyme could be used to help cure patients.

“The most important, and likely most difficult, among these is that the enzyme would need efficient and safe means of delivery and would have to be able to function without adverse side effects,” wrote lead author Indrani Sarkar of the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden.

“Nevertheless the results we present offer an early proof of principal for this type of approach, which we speculate might form a useful basis for the development of future HIV therapies,” Sarkar concluded.

LSU
06-28-2007, 05:47 PM
Sounds cool, but I'm leary of anything that would be site specific...which recombination is...mainly because it's based on DNA sequence...so eventually, if HIV alters its DNA just a smidgen, it may not be effective any longer.

Of course, one way around that is to just redesign the enzyme's specificity for the sequence. That may not be as easy as it sounds, though.

Tom Joad
06-28-2007, 08:09 PM
Very good news.

LSU
06-28-2007, 09:06 PM
Similar article from SciAm with a little more geek-talk

http://www.sciam.com/print_version.cfm?articleID=737AB56E-E7F2-99DF-382B756D1860EACA

Designer Enzyme Cuts HIV Out of Infected Cells

Bacterial enzyme turns the tables on deadly retrovirus

Scientists have constructed a custom enzyme that reverses the process by which the human immunodeficiency virus (HIV) inserts its genetic material into host DNA, suggesting that treatment with similar enzymes could potentially rid infected cells of the virus. In tests on cultured human tissue, the mutated enzyme, Tre recombinase, snipped HIV DNA out of chromosomes.

Curing real infections by this or any other technique, however, would require mastering one of HIV's sneakiest tricks—its ability to hide from the immune system by laying dormant for months or years in host cells.

HIV infects the immune system's disease-killing T cells by converting its genome into double stranded DNA and using the enzyme integrase to insert that DNA into a T cell's genome. Researchers have speculated that they could reverse this process with bacterial DNA-cutting enzymes they have adapted for adding and subtracting genes from mice and other multicelled organisms.

To take that step, researchers from the Max Planck Institute for Molecular Cell Biology and Genetics and the University of Hamburg's Heinrich Pette Institute for Experimental Virology and Immunology began with the bacterial enzyme Cre recombinase, which exchanges any two pieces of DNA flanked on either end by a certain pattern of nucleotides (DNA subunits) known as loxP.

HIV does not naturally contain loxP sites, so the team created a hybrid of the two DNA molecules, which they used to select a series of mutated Cre enzymes that were increasingly able to recognize the combined DNA. The final enzyme, Tre, removed all traces of HIV from cultured human cervical cells after about three months, the researchers report online today in Science.

"This is the first demonstration of actual removal of the integrated virus from cells," says Alan Engelman, a molecular virologist at the Dana-Farber Cancer Institute in Boston. The results are promising, he says, but researchers have to make sure the slow-acting Tre enzyme works on real-world strains of HIV and figure out how to safely and precisely administer it in gene form to give it time to snip.

Ideally, Engelman wrote in an editorial accompanying the new report, researchers would like to find a way to send Tre enzymes into the small number of T cells that carry the virus without producing new viral particles, which allows HIV to hide from both antiviral drugs and the immune system.