Request for Information: Opportunities and Challenges for Platform Vector Human Gene Therapy Trials in Rare Diseases

Notice Number: NOT-TR-17-019

Key Dates
Release Date: July 18, 2017

Related Announcements

Issued by
National Center for Advancing Translational Sciences (NCATS)


In view of recent successful human gene therapy clinical trials, the National Center for Advancing Translational Sciences (NCATS) seeks input on opportunities to increase the efficiency of human gene therapy trials in rare diseases.  In particular, we are interested in feedback regarding the use of viral vectors as platforms for therapeutic gene delivery to specific organs or cell types, and how such platforms might be developed most efficiently in clinical trials for the treatment of multiple diseases.  

Several thousand diseases affect humans, of which only about 500 have any treatment. Thanks to our growing understanding of human biology, along with the increased availability of innovative technologies, there is an unprecedented opportunity to translate scientific discoveries more efficiently into new, more effective and safer health interventions. Currently, a novel intervention can take about 14 years and $2 billion to develop, with a failure rate exceeding 95 percent.

To address the challenges, NCATS strives to develop innovations to reduce, remove or bypass costly and time-consuming bottlenecks in the translational science process to speed the delivery of interventions (e.g. drugs, diagnostics and medical devices) to patients. Rather than targeting a particular disease or scientific area, NCATS focuses on what is common across diseases and the translational process. The Center emphasizes innovation and deliverables, relying on the power of data and new technologies to develop, demonstrate and disseminate improvements in translational science that bring about tangible improvements in human health.

A substantial number of human diseases are rare monogenic disorders.  Gene replacement therapy (gene therapy) offers a potential therapeutic opportunity for most of these disorders. For many years, a major challenge facing the field has been the ability to deliver therapeutic genes to affected cell types.  However, recent results from clinical gene therapy trials have provided evidence that, at least for some diseases, this challenge has been overcome.   For example, adeno-associated virus (AAV) vectors have been used to successfully deliver therapeutic genes to the liver, retina, and brain.  Also, lentiviral vectors have been used successfully to deliver therapeutic genes to hematopoetic stem cells ex vivo, and these modified cells have been used to treat immune, hematologic, and neurologic diseases. 

Viral vectors are vehicles for delivering therapeutic genes to specific cell types.  As such, they are inherently platforms that could, in principle, be used to treat multiple diseases resulting from dysfunction in the same cell type, by substituting the relevant gene.  Given the large numbers of rare diseases, there is a compelling need for efficient strategies to rapidly adapt vectors that have been successful in one disease for the treatment of other diseases with the same target tissue. However, the current clinical trial framework does not take advantage of the inherent platform capacity of viral vectors.  Instead, current trials focus on one disease at a time, which is slow, inefficient, duplicative, and can result in delays and increased costs.  This is particularly problematic given that in many cases, funding for small rare disease gene therapy trials comes from patient advocacy group with limited financial resources.   For these reasons, the potential impact of a platform approach is greatest for rare genetic diseases.

Information Requested

As indicated above, NCATS does not focus on specific diseases, but rather on identifying solutions to challenges in the translational process that impact multiple diseases.  More efficient approaches to clinical gene therapy trials in rare diseases is an example of such a challenge. 

Therefore, NCATS seeks input on the scientific and operational opportunities, challenges, and research needs in translational science that impact platform vector gene therapy (PVGT) trials, which we define as clinical trials in which the same vector is used for multiple diseases resulting from defects in the same organ or cell type.

Some examples of interest include:

  • The most important factors limiting PVGT trials.   Such factors may include, but are not limited to: vector design, biodistribution/toxicology studies, immune responses, clinical trial design, funding mechanisms, business strategy, intellectual property, regulatory science. 
  • Implications of PVGT trials for rare disease patients / policy-makers / regulatory agencies / biotech companies / non-profit / philanthropic organizations.
  • Negative or unintended consequences to PVGT trials.
  • The existence of many rare diseases with small numbers of patients, and how this impacts the opportunities and challenges for PVGT trials.
  • Types of partnerships or collaborations that could facilitate PVGT trials.
  • Considerations and trade-offs between the development of new vectors and the use of existing vectors for PVGT trials.
  • Other strategies for accelerating human gene therapy clinical trials in rare diseases aside from PVGT trials.
  • Impediments to extrapolating clinical pharmacology, safety, or effectiveness assessments from one gene therapy trial to another when the same vector is used.

NCATS encourages stakeholders from all sectors to provide input on these and any other relevant issues. Stakeholders include, but are not limited to: rare disease patients and members of the health advocacy community; basic, translational and clinical scientists at universities and research institutions; health care providers; biotechnology, venture capital and pharmaceutical industry members; colleagues at other NIH Institutes, Centers and Offices; partners at other government agencies (e.g. the Food and Drug Administration, other agencies of the Department of Health and Human Services, and the Department of Defense); policy makers and funders; as well as the general public. Organizations are encouraged to submit a single response that reflects the views of their organization and membership as a whole.

Submitting a Response
Responses to this RFI will be accepted through September 19, 2017.  Please submit your response to, email:

Responses to this RFI are voluntary. Do not include any proprietary, classified, confidential, trade secret or sensitive information in your response. Respondents are advised that the U.S. Government is under no obligation to acknowledge receipt of the information provided and will not provide feedback to respondents. The Government will use the information submitted in response to this RFI at its discretion. The Government reserves the right to use any submitted information on public NIH websites, in reports, in summaries of the state of the science, in any possible resultant solicitation(s), grant(s), or cooperative agreement(s), or in the development of future funding opportunity announcements.

This RFI is for information and planning purposes only and shall not be construed as a solicitation, grant, or cooperative agreement, or as an obligation on the part of the Federal Government, the NIH, or individual NIH Institutes and Centers. The Government will not pay for the preparation of any information submitted or for the Government’s use of such information. No basis for claims against the Government shall arise as a result of a response to this request for information or from the Government’s use of such information.

NCATS looks forward to your input and encourages you to share this RFI document and the information with your colleagues.


Please direct all inquiries to:

P.J. Brooks, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-443-0513