Before human clinical trials can even begin, the therapeutic strategy must be tested for safety and efficacy. This is part of what constitutes our preclinical research focus at the Liu group: we develop and test gene editors in cultured cells and in animal models of human genetic diseases. Our hope is that our research results will then enable others (clinicians, regulators, companies) to develop safe and effective therapies for human clinical trials. 

That is exactly what happened in the case of pediatric leukemia patient Alyssa Tapley (BBC story here). Our group developed base editing—a precise gene-editing technology—that was then used to create an experimental T-cell leukemia therapy (BE CAR-7). This experimental therapy was the basis for the clinical trial led by Professor Waseem Qasim’s team from the University of College London (UCL). Designed as an off-the-shelf therapy, the treatment not only cleared Alyssa of her cancer cells, but has shown promise for other patients in the same trial. 

The Liu Group cannot offer medical advice or interpret test results.   

To learn more about how clinical trials work, visit: 

• Considering a Clinical Trial
• NIH Clinical Research Trials and You 

To search for relevant clinical trials, please visit: 

• https://clinicaltrials.gov/ 
• https://connect.careboxhealth.com/en-US/trials  

Please talk to your health care provider before enrolling in a clinical trial, as they can help you assess the legitimacy of the trial.   

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). 

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:

• https://clinicaltrials.gov
• https://connect.careboxhealth.com/en-US/trials 

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.

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. Prof 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):

1. Generate Cell Models — Generate human cell models with the target mutation 
2. Develop Editing Strategies — Develop gene editing strategies to correct those cells
3. Test Editing Strategies — Test on-target and off-target editing in human cell models 
4. Develop a Delivery Strategy — Integrate the most effective editing strategies with an in vivo delivery method 
5. 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
6. 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
7. Identify an organization to run the clinical trials
8. Complete IND-enabling studies
9. Finalize the candidate IND (called the “test article”)
10. Secure a manufacturer 
11. Submit an IND package to the FDA
12. Respond to FDA concerns until clearance is granted to initiate the clinical trial 

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.
• Determining the target tissues or cell types to edit. Ensuring that gene editors selectively target the cell and tissue types affected by the disease will help minimize unwanted “off-target” effects that might result from editing otherwise healthy cells and tissues.
• 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.
• 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.

The Innovative Genomics Institute or IGI has developed educational materials for anyone interested in learning more about genome editing: https://innovativegenomics.org/education/

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

A non-exhaustive list of resources is below:

• Global Genes
• Genetic and Rare Diseases (GARD) Information Center
• Genetic Alliance
• MyGene2
• Undiagnosed Diseases Network
• Rare Genomics Institute
• Rare Diseases Clinical Research Network
• National Organization for Rare Disorders (NORD)

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)

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.