“I WANT TO CHANGE THE WORLD”
To say that Professor Feng Zhang’s groundbreaking work with CRISPR is enabling other scientists to pioneer their own discoveries would be an understatement to the enormous and profound contribution this 36-year-old scientist has already accomplished during his career.
Just within the last few decades, many scientists have attempted to develop a successful method to alter human DNA with a goal to transform human lives. Today, Professor Zhang is helping to bring this reality a step closer by not only enabling the editing of the human genomes with CRISPR, but the potential to fuel other discoveries to cure and eliminate some of the world’s most devastating diseases.
The revolutionary work Zhang has done in the areas of brain science and gene editing is only a fraction of his passion to help humanity. He is equally committed to sharing his knowledge and experience to mentor others in achieving their own career goals and successes.
Thomas Edison once said, “I have not failed. I've just found 10,000 ways that won't work.” Early on in his career to present day, this same philosophy helps to capture Zhang’s tenacity and approach to his many attempts and experiments, in search of finding the perfect solution to alter the outcome of human tragedy, by ultimately curing and eliminating illness and disease. He possesses the kind of enthusiasm that is highly revered and respected by his professors, colleagues and students. The result of which has made CRISPR one of the most discussed topics among scientists throughout the world.
During our Q&A interview, Professor Feng Zhang described the foundation and differences between CRISPR-Cas9 and CRISPR-Cas13. He also provided further insight into how this technology and its evolution will alter future generations to come.
What are the significant differences between CRISPR-Cas9 and CRISPR-Cas13?
FZ: The biggest difference between these two systems is that Cas9 targets and cleaves DNA, whereas Cas13 targets and cuts RNA. DNA is often called the “blue print” for the cell – this is how genetic information is stored and passed on to future generations. DNA is read out by the cellular transcription machinery, which creates an RNA copy of certain parts of the genome. This RNA copy is used in turn as a template for building proteins. Because Cas13 works at the RNA level, it offers the potential to correct genetic mistakes without having to touch the blueprint, which may be safer. Surprisingly, despite this major difference, Cas9 and Cas13 share other similarities. For example, they both use short stretches of RNA to guide them to target sites.
How do you envision CRISPR’s evolution in the next 10 years?
FZ: CRISPR-based technologies are still very young, and with all technologies, it’s hard to predict their evolution. I’m hopeful that in 10 years, there will be a number of real-world applications for the technology that have made their mark by improving society, such as improved agricultural breeding programs, which will contribute to global food security. I think we will also see the first CRISPR-based therapeutics approved for human use in 10 years, but I think it may be longer before there is a wide-range of treatment options.
What will it (CRISPR) be capable of doing and in what ways do you see it transforming human health?
FZ: CRISPR-based technologies are already capable of a wide range of things – from accelerating agricultural breeding programs to tracking infectious disease outbreaks. I am optimistic about the future of using Cas enzymes directly as therapeutics, but I think that the biggest impact of the technology is simply speeding up the pace at which basic and biomedical research is performed. These are robust tools that are pretty easy to use, and they have been adopted by many scientists around the world. There is a huge multiplicative effect of this kind of technology sharing.
You mention that your long-term goal is to develop novel therapeutic strategies for disease treatment. Can you elaborate on these ideas?
FZ: Typically, people try to develop a medicine that treats the symptoms of a disease, and we typically tackle disease on a case-by-case basis. We are interested instead in a general treatment approach that could be used for thousands of diseases. For example, we recently developed a technology called REPAIR, which stands for RNA Editing for Precise A-to-I Replacement. REPAIR can go into cells and change a single, targeted base of RNA, such as one that is the cause of an inherited genetic disease. By reprogramming REPAIR, which we can do just by synthesizing a new guide RNA, we can correct another mutation causing a different inherited disease, and so on, for thousands of known Mendelian diseases.
What would you say are some of the most challenging aspects of your work?
FZ: One of the most challenging aspects of my work is simply finding enough time to try out all the things I want to explore. If anyone has a solution to this problem, I’d love to hear it! My approach so far has just been to go faster!
Did you have any mentors and what piece of advice did you receive that has been the most valuable to you?
FZ: When I was in high school, I had the incredible opportunity to work at the Human Gene Therapy Research Institute in Des Moines, Iowa under the mentorship of John Levy. John was amazing – he is both an extremely passionate scientist and a gifted science communicator, and he told me something that has always stayed with me. He said, “Try to stay stylish yet practical.” Almost twenty years on, “stylish yet practical” has become a guiding principle for me. It has helped dictate which problems I have tackled, it has informed the types of solutions I strive for, and I think this applies not just to the substance of problems, but also to the style in which you solve them. Above all, solutions have to be robust, reliable, and easy to use, but that doesn’t mean they can’t have style, too.
Dr. Richard Merkin is very proud of your accomplishments. As one of the first Richard Merkin Fellows, in what capacity has this support made a difference in your field of study?
FZ: I became a Merkin Fellow back in 2012, when my lab was still quite new, and the support from Richard Merkin was truly instrumental in our early success. It allowed me to spend more time with my students and post-doctoral fellows, instead of needing to spend those hours writing grants. I’ve been fortunate to have outstanding mentors throughout my career, and it’s a wonderful opportunity to start paying this back by mentoring my own students.
Feng Zhang is a core institute member of the Broad Institute of MIT and Harvard, as well as an investigator at the McGovern Institute for Brain Research at MIT, the Patricia and James Poitras '63 Professor in Neuroscience at MIT, and an associate professor at MIT, with joint appointmen ts in the departments of Brain and Cognitive Sciences and Biological Engineering.
Zhang is a molecular biologist developing and applying novel molecular technologies for studying the molecular and genetic basis of diseases and providing treatment. Zhang has pioneered the development of genome editing tools for use in eukaryotic cells – including human cells – from natural microbial CRISPR systems. He and his team have adapted multiple CRISPR systems for use as genome engineering tools, including most recently, the RNA-targeting system CRISPR-Cas13a.
Zhang leverages CRISPR and other methods to study the genetics and epigenetics of human diseases, especially complex disorders, such as psychiatric and neurological diseases, that are caused by multiple genetic and environmental risk factors and which are difficult to model using conventional methods. His lab’s tools, which he has made widely available, are also being used in the fields of immunology, clinical medicine, and cancer biology, among others. His long-term goal is to develop novel therapeutic strategies for disease treatment.
Zhang is a recipient of many awards including the Canada Gairdner International Award, the Tang Prize, the Blavatnik National Award for Young Scientists, the Albany Medical Center Price in Medicine and Biomedical Research, and the Lemelson-MIT Prize. He has also received technology innovation awards from the Paul G. Allen Family, McKnight, New York Stem Cell, and Damon Runyon foundations. Zhang is an elected member of the National Academy of Sciences.
Zhang received his A.B. in chemistry and physics from Harvard College and his Ph.D. in chemistry from Stanford University.
What is CRISPR?
Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)
It is the unique organization of short, partially palindromic repeated DNA sequences found in the genomes of bacteria and other microorganisms.
CRISPR-Cas9: A molecular scalpel that can edit or delete whole genes within the DNA structure.
CRISPR-Cas13: An RNA editing technique that can alter protein sequences without modifying the genome in a cell that can be used to reduce cancer associated gene expression.