Frequently Asked Questions
Answers to some of the most common questions we receive are listed below as a resource for patients and their loved ones. Please feel free to email us (drliuresearch@broadinstitute.
The Liu Group conducts basic (preclinical) research
The Liu group envisions a future in which people are not beholden to misspellings in their DNA that cause genetic diseases, heavily inspired by the stories of rare disease patients and their families.
As a research lab, we are working to realize this vision by conducting preclinical research. Our laboratory by itself does not conduct human clinical trials or treat patients. Preclinical research acquires the knowledge and data needed before clinical trials can be considered.
Before human clinical trials can begin, the therapeutic strategy must be tested for safety and efficacy. A focus of our laboratory is to develop and test gene editing agents—such as base editors, prime editors, and other ways of precisely modifying the genome of living systems— in cultured cells and in animal models of human genetic diseases. If promising, the resulting data can then be used to launch efforts to develop safe and effective therapies.
To learn more about how clinical trials work, visit:
To search for relevant clinical trials, please visit:
Please talk to your health care provider before enrolling in a clinical trial, as they can help you assess the legitimacy of the trial. The Liu Group does not offer medical advice.
What about the story of patients like Alyssa Tapley, baby K.J. Muldoon, Branden Baptiste, Tracy Attebury, and others?
These patients suffered from serious genetic diseases: T-cell leukemia, CPS1 deficiency, sickle-cell disease, and chronic granulomatous diseases, respectively. Our laboratory developed the base editing and prime editing technologies that were used by teams of physicians, scientists, regulators, and manufacturers to treat these courageous patients, including the first people ever treated with a base-edited or prime-edited therapeutic. In some cases, such as baby K.J. Muldoon’s case, as well as ongoing efforts to develop treatments for progeria, alternating hemiplegia of childhood, and Dravet syndrome, our laboratory participates in the process that generates data used to enable a clinical trial.
We helped found The Center for Therapeutic Genetics (CTG) [link to PR or website], a nonprofit effort involving the Broad Institute, Boston Children’s Hospital, and Jackson Labs Rare Disease Translational Center. We are hopeful that CTG will further increase our ability to bring the promise of therapeutic base editing, prime editing, and other key editing and delivery technologies to the many patients suffering from genetic disorders.
To learn more about how clinical trials work, visit:
To search for relevant clinical trials, please visit:
Please talk to your health care provider before enrolling in a clinical trial, as they can help you assess the legitimacy of the trial.
Can you explain the "Compassionate Use" and the "Right to Try" options?
Yes, we’ll do our best to help demystify these two options!
Before we do, please note that regulation in this space is evolving to keep pace with the science, so these rules may change in the future. We will do our best to keep this section of our FAQ updated, but to ensure the most up-to-date information, please cross-check the information below with your physician and the FDA’s website.
Both programs (“Expanded Access” and “Right to Try”) are for patients with a life-threatening illness who have exhausted all other treatment options and are either ineligible for a clinical trial or too far from a trial site. Both programs are a means of giving patients access to investigational new drugs (INDs), but the eligibility rules for the INDs and patients differ between the programs.
Pathway 1: The FDA’s “Compassionate Use” or “Expanded Access” option (they are the same)
Accessing the “Expanded Access” option (which can take days to weeks, depending on emergency status) requires your physician to submit an application to the FDA for approval. The FDA, together with a hospital Institutional Review Board (IRB), then reviews the request to ensure that the potential benefits to the patient outweigh the risks associated with the use of an investigational new drug (IND) and that the patient is fully informed. In contrast to the “Right to Try” option, the IND used in this pathway can be in any phase of clinical trials. || The FDA’s publication on this pathway is available here.
Pathway 2: The FDA’s “Right to Try”
The “Right to Try” option is a newer program that allows patients, their doctors, and the drug manufacturer to work together directly and removes the need to receive FDA approval. While this speeds up the process, it lacks the formal safety evaluations and dosage guidelines provided by the IRB and FDA.
A patient is considered eligible if (1) they are diagnosed with a life-threatening disease or condition, (2) have tried all approved treatment options, and (3) are unable to participate in a clinical trial to access investigational treatment options.
A drug is considered eligible if it has (1) completed Phase 1 of a clinical trial, (2) not been approved/licensed by the FDA for any use, (3) has an application on file with the FDA , and (4) is actively developed/produced (not placed on clinical hold).
How can I sign up myself/my loved one for participation in gene editing clinical trials?
While our group is working intensely on maximizing the types of genetic diseases that could potentially benefit from gene editing technologies, we do not run any human clinical trials. As a research lab, we work on the preclinical side by developing and testing gene editing agents in cultured cells and in animal models of human genetic diseases. Our hope is that the resulting research will enable scientists in industry or other clinical organizations to develop safe and effective therapeutics for gene editing clinical trials.
To read more about clinical trials and how they work:
- Considering a Clinical Trial
- Clinical Trials Process
- Understanding a Clinical Trials Listing
- NIH Clinical Research Trials and You
To search for clinical trials that are relevant to you/your loved one:
Please consult with your healthcare provider before enrolling in a clinical trial, as they can help you assess the legitimacy and appropriateness of the trial.
How long before gene editing therapies will become available for my/my loved one’s genetic disease?
Although we can’t predict exactly when gene editing will be available for each rare disease, we are encouraged by the fact that at least 25 clinical trials using base editing or prime editing are currently underway to treat diseases such as leukemias, hypercholesterolemia, alpha-1 antitrypsin deficiency, sickle-cell disease, beta-thalassemia, and chronic granulomatous disease. While there are still some important scientific issues to address, in many cases today the barriers patients face to accessing therapeutic gene editing are regulatory or economic, more than scientific. We therefore encourage rare disease patients and advocates to contact their representatives and tell their stories, and why streamlining the process of translating gene editing from bench to bedside is so important.
What is the current roadmap for developing gene editing therapeutics?
We know it is possible to translate the success of preclinical research projects from the lab to the clinic—but it’s a long and winding road in need of optimization. Professor David Liu and others recognize this challenge and are engaged with policymakers at HHS to change this reality. Until regulatory streamlining occurs, it’s helpful for patient advocates and their loved ones to understand the current roadmap so they can choose how they want to engage with moving things forward.
💡We also encourage rare disease patients and advocates to contact their representatives and ask them how they can encourage the FDA to streamline the IND requirements.💡
The current roadmap includes the following steps (infographic can be viewed here):
- Generate Cell Models — Generate human cell models with the target mutation
- Develop Editing Strategies — Develop gene editing strategies to correct those cells
- Test Editing Strategies — Test on-target and off-target editing in human cell models
- Develop a Delivery Strategy — Integrate the most effective editing strategies with an in vivo delivery method
- Test in Humanized Mouse Model — Perform in vivo editing in a humanized mouse model with the best editing system in the in vivo delivery vehicle
- Repeat steps 1-5 until the in vivo editing and delivering strategy achieves therapeutically relevant editing levels and rescues the phenotypes of the disease in the humanized mouse model
- Identify an organization to run the clinical trials
- Complete IND-enabling studies
- Finalize the candidate therapeutic
- Secure a manufacturer
- Submit an IND package to the FDA
- Respond to FDA concerns until clearance is granted to initiate the clinical trial
What scientific challenges remain?
Developing a therapeutic gene editing strategy that maximizes the therapeutic effect and minimizes the risk of unwanted side effects will also require optimizing the following parameters:
- Ideal timing of therapeutic intervention for maximal benefit. The consequence of administering a therapeutic gene editing strategy for a given disease often varies depending on the patient’s age, and the different stages of the disease. Determining the ideal time to intervene requires sufficient knowledge of disease progression.
- Safe and effective delivery methods that can route gene editing agents to the desired cells and tissues. In contrast to small molecules such as aspirin or ibuprofen, gene editors are large macromolecules that require creative delivery strategies that are more complex than swallowing a pill.
- When practical, data from animal models of the disease that demonstrate that the candidate gene editing strategy is likely to benefit the patient without any evident unacceptable risk of side effects.
- A path to manufacture the candidate therapeutic at the quality standard required for a clinical trial.
I’d like to learn more about gene editing; where can I access educational materials?
The American Society of Gene + Cell Therapy (ASGCT)’s Patient Education Program
A Glossary of Genomic/Genetic Terms by the National Human Genome Research Institute (NHGRI) https://www.genome.gov/genetics-glossary
Where can I learn more about rare diseases and/or connect with other patients and patient advocates?
How can I keep up with the latest news from the Liu group?
There are a few ways to stay up-to-date on our group’s latest happenings! Aside from visiting our publications page to freely access and download our research papers you can:
FOLLOW US on social media
- https://twitter.com/liugroup (our lab)
- https://twitter.com/davidrliu (Professor Liu)
LISTEN to one of Professor Liu’s public lectures (TED Talk; CNN’s Life Itself Lecture) or podcast interviews with Professor Liu (Theory & Practice; People Behind the Science Podcast; Bios Podcast; For Your Innovation Podcast)
READ some recent interviews with Professor Liu (The Conversation; GEN Edge; Endpoints News) or news stories written about our group’s work (press page)
Who should I contact if I have follow-up questions?
Please contact the Liu Group Manager of Communications and Outreach: Anahita Vieira (Ph.D.) via email at (avieira@broadinstitute.org) with any follow-up questions you may have.