Barb Bailus, PhD
David Gurzick, PhD

Hello Everyone!

Today we have a very special guest with us, Dr. Dave Segal! He is joining us to discuss the amazing new nine million dollar grant the University of California Davis just received to study the safety of gene editing tools. This grant is part of a much larger consortium funded through the National Institutes of Health (NIH), one of the main avenues of government funded science in the US. The Somatic Cell Genome Editing Consortium consists of multiple laboratories and centers throughout the US, all focusing on different aspects of gene editing. Focus groups range from safety, to delivery, to designing new tools. The purpose is to establish a network of labs working towards a common goal, where information, techniques and resources will be shared. The result of this combined effort will be a much more efficient and thorough characterization of potential gene editing therapies. In some ways this gene editing consortium is very much like FAST, bringing together the best minds and resources to study a current health challenge and ensure that this technology safely and efficiently reaches patients. For an overview of the entire genome editing consortium visit the official NIH site

Dr. Segal has agreed to answer some questions about both the UC Davis center and the future of gene editing as therapy.

Just a couple of clarifications for all of our readers, gene editing in this context refers to a process that changes the DNA sequence.  Gene editing is the specific focus of the Somatic Cell Genome Editing Consortium.  This is different than gene therapy which can refer to the addition of an entire gene, or changing the expression levels of a gene.

The non-human primate center at UC Davis does have non-human primates, but this does not include chimpanzees or higher level apes, as research on these animals is prohibited in the United States.

FAST: Hi Dave, many of our readers would appreciate if could you describe, what exactly is the UC Davis Nonhuman Primate Testing Center for the evaluation of Somatic Cell Genome Engineering tools?

Dr. Segal: Sure, in simplified terms the center will be testing the safety of gene editing tools like CRISPR, in large animal models. This center is an important step in evaluating the safety of gene editing tools in humans. However, before the gene editing tools are tested in large animal models such as nonhuman primates or pigs they will first be tested at a mouse core facility. This progressive testing ensures that we do not needlessly advance ineffective or potentially harmful methods.

FAST: Our readers have just finished reading about CRISPR technology in a previous blog, but they are an inquisitive bunch and have heard of some new editing tools already on the horizon, is the UC Davis center only focused on CRISPR or will it test new emerging technologies?

Dr. Segal: Great question, the gene editing field moves very quickly, five years ago CRISPR was discovered, so the next five years could hold even more amazing discoveries. The consortium’s overall goal is to be able to evaluate these new and exciting technologies as they emerge. The UC Davis Center will evaluate all technologies that the consortium is exploring. The NIH recognizes how rapidly science evolves and has not limited the program to one type of gene editing approach.

FAST: We all understand the importance of safety for these treatments, and that the UC Davis Center will be focusing on this, but will the efficacy of the different gene therapy tools or delivery methods also be evaluated?

Dr. Segal: Yes, the UC Davis center will be looking at both the safety of the gene editing technology and the efficacy of the delivery method. Some of this will include looking at the distribution of the editing tool, did it reach the desired organ, did the correct gene get edited and at what percentage. The center will also be evaluating the potential “off-target” effects of a delivery system or gene editor, this can include looking at immune response and to see what other organs received the gene editing tool and if genes in those organs were edited. These are extremely important questions to consider when designing a gene therapy, as editing in the targeted organ can be very beneficial, but in another organ could have a detrimental effect on the individual’s health. For the foreseeable future the center will focus on acute (weeks) and short term (months) response to potential gene editing therapies, but long term (years) may be necessary as gene editing therapies move into the clinic.

FAST: Can you describe the importance of the consortium and the overall impact you expect this NIH consortium to have on the gene editing field?

Dr. Segal: Absolutely! This consortium will allow for researchers in different areas of expertise to share their knowledge in a non-competitive environment with the common goal of establishing a set of guidelines for gene editing. Having this open communication between many different researchers should expedite the path toward clinical trials, and will help establish safety and efficacy measures that can be utilized by the entire gene editing field.

FAST: What is your role at the new center?

Dr. Segal: I am the Director of Genome Editing for the Testing Center. There are also directors for immunology, communications, and the Center overall. In my role, I will be using my expertise to help develop the most effective assays and technologies to evaluate the cutting edge technologies that will be tested at the Center. This is going to be a groundbreaking opportunity where innovations from across the consortium can be compared at a single location and benefit from an “honest broker” comparing one to the other. This means that reliable best practices can be established from these studies, which will bring clarity and end up helping the entire field. As my expertise expands I will be able to facilitate the most expedited and effective methods of testing and evaluating the safety of the newest gene editing strategies for therapy.

FAST: Thank you so much for describing the “big picture” of this amazing NIH program, but let’s get specific – what does this mean for the future of gene therapy for Angelman syndrome?

Dr. Segal: Right now the future for Angelman syndrome is very bright, there are multiple molecular therapy approaches being tested for potential human clinical trials. In some cases, the same kinds of methods and tools will be used as we are studying in the consortium, such as methods for getting tools into cells or the tools themselves. The NIH program will benefit AS research by helping to establish guidelines for effective and safe therapies. The establishment of these guidelines is a huge undertaking and to have such a large, diverse and distinguished group of researchers studying these questions will dramatically accelerate the path toward effective gene therapy treatments, not just for AS but for other genetic disorders. For example if one of the NIH SCGE program investigators finds an effective way to deliver gene therapy to the brain, we at the UC Davis Testing Center can provide a fair evaluation of the safety and efficiency of the method, and then share this knowledge with the entire gene therapy field. This sharing of knowledge will accelerate progress toward gene therapy treatments in patients.

FAST: Will this new NIH center and program impact your current Angelman Research?

Dr. Segal: The short answer is not right away, but as our therapeutic approach moves closer to late-stage testing we will definitely benefit from all of the new technology that the NIH program is funding throughout the country.

FAST: What are you most looking forward to in terms of this Center?

Dr. Segal: I am most looking forward to working with all the new scientists and to contribute to the development of these new and exciting gene editing technologies. I have been working in the gene editing field for over 25 years and to reflect back on the evolution of these tools is both awe-inspiring and humbling. I am honored to be part of such a groundbreaking and revolutionary program. I am very excited about where this next chapter will lead.

FAST: What do you envision as the future for gene editing?

Dr. Segal: I envision that gene editing will be at the forefront of helping treat many genetic disorders, including Angelman syndrome. I expect that we will see some fantastic new tools emerging in the next decade, gene editing tools that both cut the DNA, but are also able to repair it as a single tool, making it exponentially more efficient. The possibility of more persistent turning “on” or turning “off” genes is coming with the next generation of gene editing tools, making the need to administer the treatment less frequent as it will be longer lasting. The future looks very bright and very exciting.

FAST: Thank you so much Dr. Segal, the program sounds amazing and we are so glad that you could take the time to speak with us today.

Dr. Segal: You are welcome, I always enjoy discussing the progress toward a cure, and the exciting prospects for gene editing as therapy. I am looking forward to seeing everyone in Chicago!