Matt Gethers/20.380 HIV Project/Technical Paper/Jessie InVivo

=Jessie: In Vivo and Clinical Studies=

Introduction/Definitions

 * Purpose of In Vivo Studies/Animal Models
 * Purpose of Pre-clinical studies
 * Brief history of clinical trials

Proof of Concept - In Vivo Studies

 * Animal Model: Most likely macaque
 * Can use pig-tailed macaque with the stHIV that has a 95% similarity to HIV-1, but infection only lasts a couple months and does not progress to AIDS
 * Can be used to test prophylactic effect
 * Can use macaque model with SIVmac that will allow macaque to develop SAIDS
 * Are SIV and HIV similar enough for this to be a proof of concept?
 * Things to look at:
 * Varying doses of HSCs - what is the optimal/plausible number of engineered HSCs needed?

Pre-clinical Studies

 * Biggest concern is safety
 * Can engineered HSCs become cancerous? - Drug super-sensitivity will be helpful
 * What other safety concerns are there with regards to stem cell therapies?
 * Need to prove natural functionality of engineered HSCs
 * Differentiate properly
 * RBCs function properly
 * What else do we need to prove before getting FDA approval?

Clinical Studies

 * Phase I
 * Prove mainly safety of treatment in humans
 * Should we do similar to Koronis and divide into Ia and Ib where Ia is in healthy volunteers and Ib is in people who have failed other HIV treatments?
 * Where should we conduct our trial? US or Africa?
 * Phase II
 * Phase III