amfAR, The Foundation for AIDS Research

Gene therapy to cure HIV

Deadlines

January 12, 2017, 3:00 PM EST: request log-in credentials

January 18, 2017, 3:00 PM EST: LOI submission  
  

Request for proposals (RFP) Overview

Several barriers to the development of safe and effective gene therapy treatments overlap across disease areas. Advances made in the context of any disease may inform the development of a gene therapy-based cure for HIV.

Purpose of RFP:
Develop a gene therapy-based approach to curing HIV.

Grant topics:

1. Maximize in vivo transduction efficiency

OR

2. Optimize targeting effectiveness

OR

3. Achieve appropriate persistence of gene modifications

OR

4. Expand modified hematopoietic stem cells in vitro

Funding model
During the initial one-year funding period, grantees will compete to achieve the goals outlined in the grant topics. Those research teams that best reach the goal of each grant topic will be invited to submit a proposal for subsequent funding (ARCHE-GT), working with teams that have achieved the goals of other grant topics. ARCHE-GT grantees will be required to participate actively and cooperatively in regular conference calls and in-person meetings to share data and advance the program’s goals.

Expected outcomes
This initial one-year period of funding will be used to select research teams best suited to participate subsequently in ARCHE-GT, to be launched in 2018. The ARCHE-GT team will be expected to develop curative gene therapy product(s) that can be tested in clinical studies.

Available funding
In the initial one-year period, each grant is funded at up to $400,000 including indirect costs at a maximum 20% rate. The performance period begins on May 1, 2017, or later, and will end no later than April 30, 2018.

Eligibility
Researchers with doctoral degrees, with or without documented experience in HIV research, are eligible to apply.

Background and purpose
amfAR’s $100 million Countdown to a Cure initiative is aimed at developing the scientific basis of a cure for HIV by the end of 2020. The urgency of our goal demands that we direct our funding to studies that uncover vital knowledge directly applicable to curing HIV in people living with HIV/AIDS.

Persistent reservoirs of virus not cleared by antiretroviral therapy (ART) represent the main barrier to a cure for HIV, and amfAR expects that this RFP will solicit ideas and approaches that overcome this barrier via gene therapy. As evidenced by the “Berlin patient,” removing the reservoir and/or blocking new infection events are potential mechanisms by which a cure can be accomplished. This sole case of HIV cure strongly suggests that gene therapy may be a promising route to curing HIV.

Many potential targets − including the removal of obligate host genes, the addition of protective genes, or methods to bypass the defective immune response – have already been identified and are not the focus of this RFP. The technology to deliver gene therapy payloads requires further development and is the subject of this solicitation.

On the basis of the successful achievement of research goals during this first year of funding, amfAR intends to establish the amfAR Research Consortium on HIV Eradication - Gene Therapy (ARCHE-GT).  The goal of ARCHE-GT is to develop curative gene therapy product(s) that can be tested in clinical studies. ARCHE-GT will be a consortium of researchers whose goal is to solve the critical barriers to the development of a gene therapy-based cure for HIV.

Grant topics
In the context of this RFP, gene therapy is defined as the targeted modification of HIV or host cell DNA or RNA. The goal of these modifications is the permanent removal of HIV reservoirs.  

In June 2016, amfAR convened a meeting of gene therapy researchers to identify the most pressing barriers to a gene therapy cure for HIV. Meeting participants identified four main barriers, described below, that form the grant topics for this RFP.

Each grant funded in ARCHE-GT will address one of the following barriers:

1. Maximize in vivo transduction efficiency
One key challenge for gene therapy is the inefficiency of vector uptake, which may be even lower in the resting cells that constitute the HIV reservoir. To ensure an HIV cure, transduction efficiency will likely need to be maximized i.e., clearing all provirus or all infected cells, or preventing all new infection events.

2. Optimize targeting effectiveness
Cost and safety issues dictate that improved targeting will be required. Scalable gene therapy will almost certainly require in vivo delivery.  While some other clinical conditions may require only localized in vivo gene therapy delivery, HIV cure approaches will require targeting cells distributed throughout the body.

3. Achieve appropriate persistence
Poor engraftment and graft-versus-host disease must be overcome to cure HIV by adoptive transfer of gene-modified cells. For safety, an off-switch should be incorporated into gene modification tools.  Persistence may also be improved by maintaining gene-editing tools in the circulation and out of sinks such as the liver.

4. Expand modified hematopoietic stem cells in vitro
One HIV cure approach may consist of gene-modifying a single stem cell, for example to protect it from HIV infection, and expanding that cell to a sufficient number for transplantation, while maintaining stem-ness, gene modification(s), and the ability to differentiate appropriately in vivo into functioning hematopoietic cells.

Will be considered for funding:

  • Manipulation of existing vectors or development of new vectors
  • Non-vectored gene therapy delivery

Will not be considered for funding:

  • Discovery of new targets for gene therapy
  • Vaccine development
  • Research not directly and specifically relevant to HIV cure
  • Research whose ultimate goal is to bring about control of remaining virus, rather than removal of all pathogenic virus

If you are unsure whether your proposal fits amfAR’s grant topics, please e-mail your inquiry to grants@amfar.org.

Funding model
This initial one-year period of funding will be used to select research teams best suited to participate subsequently in ARCHE-GT, to be launched in 2018.

amfAR’s ARCHE program is characterized by interactions between teams of researchers. amfAR expects that each ARCHE-GT team will have the appropriate expertise to address one of the barriers listed above and that the design of a gene therapy-based HIV cure will necessitate collaborating with other ARCHE-GT grantee teams. The goal of ARCHE-GT will be to take a collaborative approach to applying the solutions to each of the main barriers to a gene therapy-based cure for HIV.

During the initial one-year funding period, grantees will compete to achieve one of the goals outlined in the grant topics. At the conclusion of the funding period (April 30, 2018), the progress made by each team within each grant topic will be evaluated and compared. Within each grant topic, the research team that “best” reaches the goals will be invited to submit a proposal for subsequent funding (ARCHE-GT), working with the “winning” teams that have best achieved the goals in each of the other grant topics. (The appraisal of which team has “best” reached goals may depend on the grant topic, the scientific content of the projects under evaluation, and factors such as cost, simplicity, scalability, applicability, etc.). ARCHE-GT grantees will be required to participate actively and cooperatively in regular conference calls and in-person meetings to share data and advance the program’s goals.

Expected outcomes
Grantees who do not demonstrate successful completion of the initial goals described in this RFP will not be considered for subsequent amfAR-GT funding. The ARCHE-GT team is expected to develop product(s) that can be tested in clinical studies.

Available funding
Each initial ARCHE-GT grant is funded at up to $400,000 including a maximum of 20% indirect costs. The performance period begins on May 1, 2017, or later, and will end no later than April 30, 2018. No-cost extensions will not be available.

amfAR plans to fund more than one team working on each of the grant topics. The team within each grant topic that best reaches the initial goals will have the greatest chance of qualifying for subsequent amfAR ARCHE-GT funding.

amfAR expects that grantees will leverage existing and new resources in the form of: ongoing funding from other sources; host institution resources; partnerships with teams of researchers working in non-profit or for-profit settings; and other resources that promote the achievement of grant goals. Applicants should describe these resources and how they will complement the funding and team resources offered by amfAR.

Eligibility
Researchers with doctoral degrees, with or without documented experience in HIV research are eligible to apply. All proposed research must be directly and specifically relevant to developing a cure for HIV. Researchers who are new to HIV are strongly advised to work closely with an HIV cure research expert and to consult existing literature on gene therapy for an HIV cure during the formative stages of the research plan. Further details regarding eligibility can be found in the application instructions.

Selection process
Each applicant will submit a Letter of Intent (LOI) that will be reviewed by 3 peer reviewers. Feedback to applicants, although limited, will be provided to all. On the basis of peer reviewer enthusiasm for the proposal, and amfAR’s desire to fund more than one team working on each grant topic, amfAR will solicit full applications from a subset of LOI submissions. Full applications will be peer reviewed by experts in HIV cure research and/or gene therapy, and written reviews will be provided to all applicants. amfAR will prioritize submissions describing transformative research plans.

Investigator responsibilities
Depending on peer review and amfAR program priorities, program staff may work with applicants to modify the submitted work plan and/or budget. Submission of an LOI to amfAR in response to this RFP will be interpreted as an expression of interest in participating in ARCHE-GT. In the event that the applicant is invited to join ARCHE-GT after the first year of funding, amfAR expects that the grantee will share relevant findings and will work collaboratively with other members of the ARCHE-GT team. Additional details about ARCHE-GT will be provided when applications are solicited in late spring 2018.

Requesting LOI Application Forms and Credentials
Submission of Letters of Intent is a two-step, online process.

  • You must request log-in credentials no later than 3:00 p.m. EST on Thursday, January 12, 2017.

  • CLICK HERE to request log-in credentials. Username, password and a link to the submission portal will be sent to the email address provided.

    Be aware that it generally takes one business day to process credential requests. If credentials are requested on a Friday, they may not be sent until Monday.  Also note that credentials requested December 22 through December 26 may not be sent until Tuesday, December 27; credentials requested December 30 through January 2 may not be sent until January 3.    

  • Use the log-in information to complete and submit the LOI online through the portal. LOIs must be submitted via the portal no later than 3:00 p.m. EST on Wednesday, January 18, 2017.

Please be sure to request credentials and forms with adequate time to prepare a Letter of Intent. Deadline extensions will not be provided.

Other Important Dates (all dates are tentative)
Invite full applications: February 10, 2017
Full applications due: March 13, 2017
Performance period begins: May 1, 2017