The CRISPR Revolution
CRISPR (Clustered Regularly Interspaced Short Palindormic Repeats) has taken the healthcare, biotech, and academic worlds by storm. The technology has already been used to repair defective DNA in mice and to edit genes in crops. Ultimately, the precise nature of the genome-editing tool has tremendous potential to lead to many treatments and cures for patients.
On June 29th, MassBo hosted two standing room only panels on the opportunities and challenges targeted genome editing presents. The panels couldn’t have been more timely with an article published just the day before by the Wall Street Journal on CRISPR and why it has scientists so excited.
Panelist Tom Barnes, Chief Scientific Officer at Intellia Therapeutics echoed the article when he shared his thoughts on the new tool:
"Although gene editing has existed as a new therapeutic modality for a little while, the advent of the CRISPR/Cas 9 system has resulted in an explosion of activity in academia and an explosion of interest in editing in industry. Academics are drawn to its reliability, speed, and low cost, while in industry we are drawn to its simplicity, efficacy and accuracy.” – Tom Barnes
Dr. Barnes was one of several industry and academic panelists. The full list included:
- Tom Barnes, PhD, Chief Scientific Officer, Intellia Therapeutics
- Katrine Bosley, Chief Executive Officer, Editas Medicine
- Bill Lundberg, MD, Chief Scientific Officer, CRISPR Therapeutics
- Scott Gillis, Principal, Pharmaceutical and Medical Device Consultation, CEO, Onsite Therapeutics, Inc. (Moderator)
- George Church, PhD, Professor of Genetics, Harvard Medical School
- Chad Cowan, PhD, Associate Professor, Harvard University Department of Stem Cell and Regenerative Biology
- Erik Sontheimer, PhD, Professor of Molecular Medicine, University of Massachusetts Medical School
- Bruce R. Zetter, PhD, Charles Nowiszewski Professor of Cancer Biology, Department of Surgery, Harvard Medical School (Moderator)
The first panel covered optimal disease candidates, ethical dilemmas surrounding the technology and more. Read on to hear some of the big questions addressed.
What is the ideal candidate for CRISPR?
The panel suggested monogenic diseases that have both a high unmet need and high severity level are good candidates for CRIPSR/Cas 9.
What is so special about CRISPR?
“I tried it and my first experiment worked!”- Katrine Bosley
According to Katrine Bosley, CEO of Editas Medicine, this is what scientists are saying across the board. In the biotech industry, experiments often fail. It is refreshing to handle a tool that consistently does precisely what it’s supposed to do.
CRISPR/Cas 9 also boasts an ease of use. The technology has received more attention than previous tools such as Meganucleases, Zinc Finger Nucleases, and Transcription Activator-Like Effector Nucleases (TALENS), because of the ease of gene editing compared to the other tools that require complex genetic engineering or molecular cloning to re-target the nucleases. With CRISPR/Cas 9, you only need to change a small portion of the sequence accompanying the RNA guide molecule. You can also potentially make multiple double stranded breaks (DSBs) in the same cell, also called Multiplexing via CRISPR
What is the ethical dilemma and where does the industry stand?
CRISPR/Cas 9 will allow scientists to manipulate the human genome. This has the potential to lead to treatments and cures but also presents major ethical dilemmas.
Recently, scientists in China at Guangzhou University used CRISPR/Cas 9 on triploid embryos which have three sets of genes instead of two, essentially making them non-viable embryos, to carry out germ line gene editing. This has sparked a conversation surrounding the ethics of the tool.
When reflecting on the panel, Tom Barnes remarked:
"Germ line modification is not supported by any of the companies, and all were keen to see a broad-based conversation take place so that society as a whole comes to an understanding and comfort with what it collectively wants to do.” – Tom Barnes
Germ line modification, or the genetic engineering of human embryos, was unanimously opposed by the panel. As this revolutionary tool becomes closer to reality, the panel agreed that there needs to be a larger conversation to discover how far the human race is willing to take CRISPR.
What is the future of CRISPR?
In ten years, the panel has aspirations to master targeted alterations, jump the regulatory hurdles, understand the economic implications of CRISPR/Cas 9 technology, and most importantly, cure patients.
The second panel provided insight from the academic perspective and expanded upon some of the topics covered in the first panel.
What is one of the biggest challenges that CRISPR presents?
"You need to hit where you want to hit and not anywhere else. And that’s a difficult problem to solve.” – Erik Sontheimer
Erik Sontheimer, Professor of Molecular Medicine at University of Massachusetts Medical School presented off-targeting as a major challenge that must be overcome to move forward with CRISPR/Cas 9 technology. Precision is key when editing the genome.
What is the future of CRISPR?
The panel had a grand vision for the future of CRISPR. George Church, Professor of Genetics at Harvard Medical School expects to see increased specificity and multiplexing. His record thus far is 62 changes at once!
Chad Cowan, Associate Professor at Harvard University’s Department of Stem Cell and Regenerative Biology, believes the technology is going to help uncover disease drivers.
"We’re not talking therapy anymore. We are talking cures.” – Chad Cowan
The panelists provided a great discussion with a wealth of valuable information on this new and exciting scientific advancement. Panelist Erik Sontheimer provided final thoughts on the event:
"The discussions of both MassBio panels (company and academic) provided vivid illustrations of why CRISPR technology is causing so much excitement, and why CRISPR science is so fascinating. Even the panelists learned a tremendous amount about the opportunities and challenges ahead, and it was clear that the audience learned even more. I look forward to more events like this in the coming years.” – Erik Sontheimer