posted on Sep, 17 2007 @ 11:20 AM
Very exciting news, but experimentation with Tre Recombinase has been going on for awhile now in German labs. It is a very promising approach to HIV
gene therapy, but there are a number of hurdles before this can be used to effectively treat HIV+ individuals. Let me describe what exactly is going
on with this particular enzyme and why this may be very beneficial to HIV research.
HIV contains mRNA as its basic genome before Reverse Transcriptase converts it into DNA upon entering a host cell. This DNA is then integrated into
the cell through Integrase where it enters a short latency period before exiting the cell and starting a larger infection. Now, HIV contains multiple
genes within its genome such as GAG, POL, ENV, VIF, etc. that are surrounded by Long Terminal Repeats (LTR) which mediate integration of the
Lentivirus DNA into another part of the chromosomes. This process is the key to understanding how the Tre enzyme works. Tre Recombinase (enzyme) can
remove viral DNA from the host because they allow specific genes to be removed from the region of the HIV LTR's. Once the viral DNA is removed
cellular function should be restored, and the cell should be able to integrate its own DNA back in the genome. Gene therapy such as this, should it
be developed effectively, could very well pave the way for removal of HIV DNA once past Reverse Transcriptase.
Some problems that might hinder the research include:
1. Tre and Cre Recombinates are easily destroyed by the bodies natural Immunological properties, and one's own body will actively seek them out.
2. Both enzymes act very slow when introduced into the body. This means that to aviod being destroyed they must be engineered and manufactured to
act more quickly.
3. Cultured cells being exposed to Tre is a very different process than being exposed in real world situations. Only if this therapy makes it into
the clinical trial stages will we know if it will be effective as a treatment option.
The specific enzyme Tre Recombinase was actually developed from another enzyeme found in Bacteriophages (viruses which infect bacteria) called Cre
Recombinase. Specific proteins found inside this enzyme catalyze the interconversion of polymers to have an effect on the topology of DNA structure.
In other words, it basically works to cut out certain parts of DNA and can alter the topology of it as well. The easiest way to visualize this
process is that Tre Recombinase is able to snip out specific sequences known as LoxP (abbreviation for "Locus of X-over P1" and the site for DNA
recombination within a molecule) where Recombination can occur.
Due to the fact that research into the uses of this enzyme are so new, it will be a number of years until clinical trials and such can be conducted to
assure positive use for Tre in gene therapy for HIV+ people, but early signs do show a positive slant.
[edit on 17-9-2007 by Jazzerman]