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Partnership to Expand Effective Gene Therapies for Rare Diseases

Posted on by Dr. Francis Collins

DNA strands in adenovirus shells. Silhouettes of children are on the right.

Rare diseases aren’t so rare. Collectively, up to 30 million Americans, many of them children, are born with one of the approximately 7,000 known rare diseases. Most of these millions of people also share a common genetic feature: their diseases are caused by an alteration in a single gene.

Many of these alterations could theoretically be targeted with therapies designed to correct or replace the faulty gene. But there have been significant obstacles in realizing this dream. The science of gene therapy has been making real progress, but pursuing promising approaches all the way to clinical trials and gaining approval from the U.S. Food and Drug Administration (FDA) is still very difficult. Another challenge is economic: for the rarest of these conditions (which is most of them), the market is so small that most companies have no financial incentive to pursue them.

To overcome these obstacles and provide hope for those with rare diseases, we need a new way of doing things. One way to do things differently—and more efficiently—is the recently launched Bespoke Gene Therapy Consortium (BGTC). It is a bold partnership of NIH, the FDA, 10 pharmaceutical companies, several non-profit organizations, and the Foundation for the National Institutes of Health [1]. Its aim: optimize the gene therapy development process and help fill the significant unmet medical needs of people with rare diseases.

The BGTC, which is also part of NIH’s Accelerating Medicines Partnership® (AMP®), will enable the easier, faster, and cheaper pursuit of “bespoke” gene therapies, meaning made for a particular customer or user. The goal of the Consortium is to reduce the cost of gene therapy protocols and increase the likelihood of success, making it more attractive for companies to invest in rare diseases and bring treatments to patients who desperately need them.

Fortunately, there is already some precedent. The BGTC effort builds on a pilot project led by NIH’s National Center for Advancing Translational Sciences (NCATS) known as Platform Vector Gene Therapy (PaVe-GT). This pilot project has helped to develop adeno-associated viruses (AAVs), which are small benign viruses engineered in the lab to carry a therapeutic gene. They are commonly used in gene therapy-related clinical trials of rare diseases.

Since the launch of PaVe-GT two years ago, the project has helped to introduce greater efficiency to gene therapy trials for rare disease. It’s also offered a way to get around the standard one-disease-at-a-time approach to therapeutic development that has stymied progress in treating rare conditions.

The BGTC will now continue to advance in-depth understanding of basic AAV biology and develop better gene therapies for rare and also common diseases. The consortium aims to develop a standard set of analytic tests to improve the production and functional assessment of AAVs and therapeutic genes. Such tests will be broadly applicable and will bring the needed manufacturing efficiency required for developing gene therapies for very rare conditions.

The BGTC also will work toward bringing therapies sooner to individuals in need. To start, BGTC-funded research will support four to six clinical trials, each focused on a distinct rare disease. While the details haven’t yet been decided, these diseases are expected to be rare, single-gene diseases that lack gene therapies or commercial programs in development, despite having substantial groundwork in place to enable the rapid initiation of preclinical and clinical studies.

Through these trials, the BGTC will chart a path from studies in animal models of disease to human clinical trials that cuts years off the development process. This will include exploring methods to streamline regulatory requirements and processes for FDA approval of safe and effective gene therapies, including developing standardized approaches to preclinical testing.

This work promises to be a significant investment in helping people with rare diseases. The NIH and private partners will contribute approximately $76 million over five years to support BGTC-funded projects. This includes about $39.5 million from the participating NIH institutes and centers, pending availability of funds. The NCATS, which is NIH’s lead for BGTC, is expected to contribute approximately $8 million over five years.

Today, only two rare inherited conditions have FDA-approved gene therapies. The hope is this investment will raise that number and ultimately reduce the many significant challenges, including health care costs, faced by families that have a loved one with a rare disease. In fact, a recent study found that health care costs for people with a rare disease are three to five times greater than those for people without a rare disease [2]. These families need help, and BGTC offers an encouraging new way forward for them.


[1] NIH, FDA and 15 private organizations join forces to increase effective gene therapies for rare diseases. NIH news release, October 27, 2021.

[2] The IDeaS initiative: pilot study to assess the impact of rare diseases on patients and healthcare systems. Tisdale, A., Cutillo, C.M., Nathan, R. et al. Orphanet J Rare Dis 16, 429 (2021).


FAQ About Rare Diseases (National Center for Advancing Translational Sciences/NIH)

Bespoke Gene Therapy Consortium (BGTC)

Platform Vector Gene Therapy (NCATS)

Accelerating Medicines Partnership® (AMP®) (NIH)

NIH Support: National Center for Advancing Translational Sciences; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Eye Institute; National Heart, Lung, and Blood Institute; National Human Genome Research Institute; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institute of Dental and Craniofacial Research; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; National Institute on Deafness and Other Communication Disorders; and NIH’s BRAIN Initiative.


  • Theodore Roumel says:

    Francis: This has been a long time in coming. A benchmark event in dealing with rare diseases. Thanks. Ted Roumel

    • Anastasia says:

      How does this reconcile with Darwin’s theories on evolution? I am sure there are plenty of family lines interested in the role of chromosome 10. Historically some branches of these family have become extinct. Economically orphan diseases are not that feasible unless they are subsidized and get fast-tracked for development. That usually involves lobbies by patient advocacy groups and then obviously it becomes of interest who supports those lobbies. What a tangle we live in.

      • Kleiner bottle says:

        Medical research is not cheap. While $76M can seem astronomical to a lay person, one should ask California voters about the proposition that injected $3B for stem cell research in 2004. Subsequently got refunded by California voters in 2020 for an additional $5B. No approved products. Many may question the ROI, but sufficient numbers seem to also think investment is not always about “move quick and break things”.

  • Robert Luke Nussbaum says:

    Dear Francis: The BGTC is a great step forward. What I do not see anywhere in this blog posting, however, is a crucial element of making this work: having a system for rapidly identifying and characterizing, at the molecular level, the patients who would be eligible for trials and, ultimately therapy. Particularly, in rare disorders, patients remain undiagnosed or diagnosed late when much damage has already occurred. The BGTC puts a lot of emphasis on therapy but very little on diagnosis and case finding.

  • Ann Graham says:

    Very exciting! Thank you for taking on this monumental task. There are many components to targeted gene therapy, not the least of which is ethical. Many more to be revealed, dealt with and overcome. Every journey begins with a single step – through collaboration and meaningful partnerships, we will arrive at Better for humanity.

  • Sara says:

    Dr. Collins: This is very exciting and hopeful news for a parent of a child who was diagnosed with a rare genetic disease this year. How will the BGTC decide which rare diseases it will target? How can the public stay up to date on progress and findings? With much gratitude, Sara

  • Zuccheri Gianni says:

    What Dr. Collins illustrates also brings us to some good news that we read with pleasure:
    last October ten children regained their sight thanks to gene therapy, voretigene neparvovec, for hereditary retinal dystrophies.
    The treatment was carried out at the hospital of the Vanvitelli University of Naples. A therapy, for a form of hereditary retinal dystrophy, that is linked to mutations in both copies of the RPE65 gene.
    It is reported that years ago the phase I trial was carried out thanks to the collaboration between the Vanvitelli University, the Telethon Foundation and the Children Hospital of Philadelphia.

    When the dream of healing becomes reality:
    the sight of a child rekindled is like the beauty of a star that appears in the sky.

  • F.P. says:

    It is a great news for the people who are suffering from many kind of rare diseases.Thank’s everyone for your hard work.

  • EDITH V. says:

    This post was truly worthwhile to read. I wanted to say thank you for the key points you have pointed out as they are enlightening.

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