New Anti-HIV Gene Therapy Makes T-Cells Resistant to HIV Infection

[Inchlingblue]

New Anti-HIV Gene Therapy Makes T-Cells Resistant to HIV Infection

An innovative genetic strategy for rendering T-cells resistant to HIV infection without affecting their normal growth and activity is described in a paper published in Human Gene Therapy, a peer-reviewed journal published by Mary Ann Liebert, Inc.

PRLog (Press Release) – Jan 26, 2011 – Contact: Vicki Cohn, Mary Ann Liebert, Inc, (914) 740-2100, ext. 2156, vcohn@liebertpub.com   

New Rochelle, NY—An innovative genetic strategy for rendering T-cells resistant to HIV infection without affecting their normal growth and activity is described in a paper published in Human Gene Therapy, a peer-reviewed journal published by Mary Ann Liebert, Inc. (http://www.liebertpub.com). The paper is available free online at http://www.liebertpub.com/hum


A team of researchers from Japan, Korea, and the U.S. developed an anti-HIV gene therapy method in which a bacterial gene called mazF is transferred into CD4+ T-cells. The MazF protein is an enzyme (an mRNA interferase) that destroys gene transcripts, preventing protein synthesis. The design of this mazF gene therapy vector ensures that synthesis of the MazF protein is triggered by HIV infection. When HIV infects treated T lymphocytes, MazF is induced, blocking HIV replication and, essentially, making the T-cells HIV resistant.

This elegant gene therapy tool was developed by Hideto Chono and colleagues from Takara Bio Inc. (Otsu, Shiga, Japan), Seoul National University and ViroMed Co. (Seoul, Korea), National Institute of Biomedical Innovation (Tsukuba, Ibaraki, Japan), and Robert Wood Johnson Medical School (Piscataway, NJ). The authors describe the theory and science behind this strategy in the paper entitled, “Acquisition of HIV-1 Resistance in T Lymphocytes Using an ACA-Specific E. coli mRNA Interferase.”


Continued . . .

LINK:

http://www.prlog.org/11251889-new-anti-hiv-gene-therapy-makes-cells-resistant-to-hiv-infection.html
 

[Cosmicdancer]

Thanks for posting Inch.

Here's a link to the pdf of the 9 page study if you feel like trying to wade through a technical document.

http://www.liebertonline.com/doi/pdfplus/10.1089/hum.2010.001

[Inchlingblue]

Thanks, I like reading technical literature. They focus on the fact that this procedure makes T cells resistant to HIV which, of course, is amazing. I'm wondering, though, whether HIV can develop resistance around MazF.  I guess not, since this procedure entails a change made to the host and not evolutionary pressure on the virus itself?

[surf18]

but it doesnt eliminate the virus as much as the anti v's do right?
it saves the tcells put the virus is still in the bodies by the millions or whatever?

[Inchlingblue]

but it doesnt eliminate the virus as much as the anti v's do right?
it saves the tcells put the virus is still in the bodies by the millions or whatever?

HIV uses T cells in order to multiply. If the virus is not able to attack the T cells eventually it dies out. It has nowhere to go.

[coolstone25]

HIV uses T cells in order to multiply. If the virus is not able to attack the T cells eventually it dies out. It has nowhere to go.

Hello Inching

The question surf posited was quite specific. The second last sentence in the abstract paragraph of the paper answers that question - the provirus indeed remains in the host cells unexcised. What this method does is, it prevents HIV-1 replication within the cells and suppresses the translation part by "destroying" the HIV-1 mRNA. This would be, what I'd say, is a 'functional' cure. It still remains to be seen, how well this would work in a macromodel; If the gene insertion is deleterious or causes functional gene interruptions OR if this Tat dependent mazF (ACA-less) gene is inserted at sites which have lower transcription rates, it might just reduce viral load than completely stop it;

Delivery to all affected cells and reservoirs(even behind the blood brain barrier) is still the problem as far as i understand;

This research is headed the right way - using HIV-1 proteins as transducing and/or activating transcription factors for expression of specifically built sequence cassettes against HIV or anti-HIV encoding genes(could be for specific enzymes or siRNA or RNASE based therapy).

I was trying to download this as a PDF, do you folks know how to get it online in PDF format?

[coolstone25]

Oh geez, sorry, I had completely missed the PDF link already in this thread. Thanks inchling - and to you cosmic for the PDF (strangely I was pulling an HTML version all the time.)

[hahaha]

how long will this be commercialized?

[coolstone25]

Typically, it takes atleast 10-15 years of encouraging results and passing all stages of trials with demonstration of significant reduction of viral load or enhanced protection against infection and safety standards and delivery to targeted cells - through preclinical and clinical trials - for such experimental therapeutics to reach the market.

Experimental therapies are not as 'fast tracked' as AZT was approved in the 80s.

But if I have it right, all the different therapies should be in a big cooking pot of futuristic therapies that we are discussing today, on the market within 15 years and I completely believe functional cure is a true reality for the new positives. The therapies in experimental stages we see today, (taken with meds or in other cases without) are also highly protective against new infections or atleast, reduce new infections as well as in bringing down viral loads very significantly. Data is being reported in many studies... tune in for abstracts from the CROI 2011 at boston going on right now, if you aren't in boston already.

[surf18]

Ok this brings me to a question I have. We are reading about all these great things coming to us possibly many years from now. Ok fine
But where are the magic cures and stuff that was being developed years ago? Shouldn't there be things that would work that are out now? Or is technology just finally figuring out things that might cure this thing?

[coolstone25]

Oral medications - your inhibitors - or even experimental vaccines etc in development had raised concerns about very difficult side effects, deaths and low protection/effectiveness. Many failed in clinical trials. However our understanding at the molecular level and mechanisms is much better now - the progress made in last 10-15 years was huge. Our technology is much better now and the tools of knowledge we have are better too. In 15 years new positives can look forward to therapies without any undesirable side effects, like liver/kidney functions being impaired or hit.... the new therapies wont be hard on their bodies and they shall be functionally cured. Lipodystrophy shall be a thing of past.