The recent news that the Nobel Prize in Chemistry has been awarded to Emmanuelle Charpentier and Jennifer Doudna for their seminal discovery in 2012, the CRISPR-Cas9 gene editing tool, shows the impact the technology has had on the life sciences, with many potential applications in medicine and in agriculture.
Research labs quickly picked up the tool for experiments. It also triggered the development of innumerable startups, which have attracted hundreds of millions of dollars in investment in search of new cancer, hemophilia and cystic-fibrosis treatments.
In a webinar yesterday, gene editing pioneer, Dr Eric Kmiec, director of the Gene Editing Institute at ChristianaCare’s Helen F Graham Cancer Center, discussed the broader implications of the use of CRISPR.
He spoke about an upcoming lung cancer trial, relying on CRISPR, led by his Delaware, USA-based institute, and also acknowledged the Nobel Prize win.
“CRISPR in bacterial cells was known for many years but Emmanuelle and Jennifer democratized it, they brought forward the CRISPR idea. There is also recognition of two women winning the Nobel prize solely, without a man being attached, and we certainly appreciate that.”
CRISPR based COVID-19 diagnostic testing
Like many other CRISPR labs, when the COVID-19 pandemic hit, Kmiec’s institute started evaluating CRISPR-based diagnostic tools. “We have been particularly focused on the SHERLOCK and DETECTR tests, which come from MIT and [the University of California] Berkeley and associated companies.”
These CRISPR based tests have great potential for point-of-care diagnosis as they work well and are relatively easy to use; moreover, they do not require complex instrumentation, he said.
“What we have contributing to the field is [our work looking at] other types of COVID-19 variations that are likely coming. If you look at the epidemiological data of viral infections around the world, there are variants all the time. And, obviously, as a virus emerges into the human population, it changes and mutates, so we are making sure that CRISPR diagnostic tests are going to be able to detect the virus we have now but also the next wave of COVID-19 and other associated viruses.”
Advances in therapeutic application of CRISPR
In terms of supporting the evolution of CRISPR-based medical treatments, the gene editing pioneer said the institute continues to work, with funding from the US National Institutes of Health (NIH) and various foundations, on teasing the basic mechanisms of CRISPR apart and finding its weaknesses, then feeding that knowledge into drug and therapeutic development.
"Everyone talks about the strengths of CRISPR and the associated off-site mutagenesis but there are some other peculiar things that CRISPR does that we've been able to discover and move forward."
And understanding the full picture in terms of the gene editing tool, quantifying the diversity of genetic outcomes, is critical for moving CRISPR to therapeutic application, he said.
“We want to correct mutations in sickle cell disease, we want to effectively knock genes out that are causing chemotherapy resistance in cancer cells. But, in fact, we also want to understand what else CRISPR does, what the rest of the story is."
To do that, the team has developed its own software tool, called Decoder. "We are now actively shopping for licenses and have a few clients that are probably going to license it. It shows that not only are we in mechanism and regulation mode, but we are tool makers as well, and that, if we have something that we need, we will go and make it. It is teaching us to be self-sufficient but also not afraid of the answers."
There are tremendous obstacles to using CRISPR therapeutically, stressed the scientist.
“A lot of the work in the gene therapy world has come up a bit short; we have learnt a lot, and that is important, but we believe that CRISPR is going to be most effective in the therapeutic realm if it can disable genes that are causing chemotherapy resistance. We have been working for the past 18 months on that and we had our first formal meeting with the US Food and Drug Administration (FDA) last Thursday.
"The FDA has provided us with guidance to come down the home stretch… and it suggested that [our approach] might not only be a specific treatment for squamous cell carcinoma, which is a major form of lung cancer, but could also be used as a platform for other forms of cancer such as esophageal.”
In a groundbreaking partnership, the Gene Editing Institute, along with Delaware Technical Community College and Rockland Immunochemicals Inc, have announced a move to market and sell an educational kit, CRISPR in a Box, globally.
CRISPR in a Box is designed for use in educational sessions in high schools, community colleges, universities and companies and is also suitable for remote learning.
The partnership is likely the first-ever collaboration among scientists, educators and a life-science company to train the next generation of genetic scientists and technicians in the revolutionary CRISPR gene-editing technology.
But Kmiec wants to go one step further in terms of educating students.
He believes that sickle cell disease, which is more common in certain ethnic groups, can be cured by CRISPR.
“So we're putting together a program that not only talks about gene editing and using CRISPR in a Box to demonstrate [the technique] but also asking why sickle cell disease has remained uncured. Is it because these diseases don't affect the mainstream culture? We're going to engage in those kind of conversations [with students] because we have the courage to do so. We'll also be providing them with a bird's eye view of our own work, as we just received US$1m grant to continue looking at the diversity of responses of African American regenerative cells to various forms of CRISPR and we're going to let the students follow us along, hopefully by a weekly or bi weekly live stream.”
Broadening DNA research
Ethnic diversity is an important consideration as studies continue on the new gene technologies, said the scientist.
The underlying genetic sequence among different races and ethnicities is often different, and the vast amount of DNA in the research database is from people of European descent, said Kmiec, when talking to local outlet, Delaware Public Media, in February.
“If we’re going to develop universal therapies, where breakthrough therapies reach minority communities, which is our major objective here, we’re going to have input from minority groups to be able to build those databases so we can devise the tools to actually make them work in a universal way—the whole population."