Please find below the action items from the RF2 meeting on December 7, 2022. If you have any questions about the meeting or action items please reach out to Dr. Nadia Roan and Dr. Lish Ndhlovu.
Today we discussed the strengths and weaknesses from the SAB report. RF2 has done very well and the SAB did not really point out many weaknesses. One note they made was that “some candidate Tat inhibitors have EC50s in the low micromolar range and seem good candidates for optimization. However, this will require outside resources in order to pursue synthetic chemistry on several leads.”
HOPE investigators will discuss with NIH program officers about potential strategies and resources to help with additional drug screening. We plan to speak with Betty Poon and Gerard Lacourciere with the NIH during the Miami meeting to discuss tat-inhibitors. We could also discuss with Chris Lambros from NIAID, Avi Nath from the NIH, or Persilla Yang from Stanford about chemical biology, degraders, and protac viral targets.
Chris Lambros, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
The next round of applications is due Jan 2023 to the Department of Health and Human Services that are internally reviewed.
HOPE investigators will reach out to Sara and Davey at the Last Gift cohort to go over potential clinical trials (combined dCA and spironolactone, Rapamycin, Brec, etc.). Clinical trials would need to be funded outside the UM1. One potential funding source would be the ACTG: Request for Applications- Small Clinical Trials Advancing HIV Remission and Cure (ACTG RFA). We will look at XPB degradation and Susana will discuss potential spironolactone trials to the ACTG.
Ulrike is working with Francisco on Aim 3 using CRIPSR-based approaches. Melanie is working on dead Brec domains, but we don’t know if the effect is interfering or if this is long-lasting repression that changes the chromatin. Looking at Martin’s old work (Greene Lab), Fran is working on chromatin modifications at the LTR. We can deliver brec 1 with AV (RF3) using specific delivery methods to CD4 cells, nanobodies fused AV and higher concentrations. Priti is receiving a third batch of AAV to test on humanized mice. There is a challenge to get transgenes into T-cells lines. Other lab updates include Brazil getting their first enrollment of a patient using spironolactone.
Susana Valente – Coordinate with Betty Poon and Gerard Lacourciere with the NIH during the Miami meeting to discuss tat-inhibitors.
We can connect VHL to certain binders, but how do we prove which components are binding and then develop a protac. We will coordinate with Niren to make them more permeable and maintain deficiency and solublability.
HOPE meetings with Last Gift
We will look at XPB degradation and Susana will give a talk about spironolactone to the ACTG.
Denise – Send nonhuman primate studies/ PK experiment plan to the group soon
Ana Leda – give DNA to Lish to look at the methylation state.
If you are attending the Miami Meeting and would like to join the HOPE dinner on 12/12 Please let Robert and me know.
The HOPE Collaboratory-wide meeting is on January 17th. We will hear from all the RFs. Ulrike and Fran may be presenting for RF2 (12-minute presentation, 8-minute discussion).
The next RF2 Meeting is February 1st. Please come prepared with some updates.
Please Acknowledge HOPE & the NIH in any publications or presentations and notify the Program Manager. Here are some examples of what you can include.
“Research reported in this publication was supported by the NIAID of the National Institutes of Health under award number UM1AI164559, with co-funding support from NIDA, NIMH, NHLBI, the NIDDK, and the NINDS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”
“This research was supported by NIAID award number UM1AI164559, co-funded by NHLBI, NIDA, NIMH, NINDS, and NIDDK.”