Potential new anti-HIV therapy: SEEK AND DESTROY!

Fun! I like this new idea!

Targeted Cytotoxic Therapy Kills Persisting HIV Infected Cells During ART

I havent talked about 'scFv' on ERV yet, but theyre very handy tools scientists are taking advantage of more and more these days.

'scFv's are single-chain variable fragments... not an overly useful name, but what they are are basically the recognition domain of an antibody. Normally the recognition portion of an antibody (what says 'stick to HIV!' or 'stick to influenza!') is made up of the variable regions of two parts of the antibody-- the Heavy and Light chain.

An scFv turns that recognition domain into one small protein (not two parts of two large proteins).

From there, you can paste that scFv on to whatever you want!

Scientists have used them previously for CARs to treat cancer-- use the recognition domain of an antibody (in this case, the antibody recognizes CD19 on the surface of tumors), turn it into an scFv, and put the scFv on the end of a cytotoxic T-cell signaling domain to make cytotoxic T-cells that kill tumors.

In THIS paper, the attached an scFv made from an anti-HIV antibody (anti-Env) to a bacterial toxin.

In theory, these are little anti-HIV grenades! They would attach to the surface of HIV infected cells via the expression of Env on the surface of infected cells, and deliver a 'bomb' that stops protein synthesis of the cell!

Stop protein production in an infected cell, stop viral production in an infected cell.

LOVE IT!

In this paper, they tried this hypothesis out in humanized mice (mouse with a 'human' immune system). Not a perfect small animal model, but its what we have.

They infected mice with HIV, and gave them HAART, with or without their new therapy.

Drop in viral RNA from infected cells (not free-floating virus, remember this targets infected cells!) in all tissues. This is good, as it means their therapy gets where it needs to go, though it doesnt look like they looked in the CNS:

http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppa…

Whats fun, is, they could add any number of toxins to the tails of their scFv, or they could add any scFv to their toxins.

After optimization, this could be a really exciting new therapy!