CRISPR And Reddit: Doudna Hosts “Ask Me Anything” Session
By Bio-IT World Staff
January 19, 2018 | Yesterday, Jennifer Doudna Professor of Chemistry, Biochemistry, and Molecular Biology at the University of California, Berkeley hosted an “Ask Me Anything” (AMA) session on Reddit with assistance from her colleagues at Doudna Lab and at the National Human Genome Research Institute (NHGRI).
The occasion for the AMA was the NHGRI awarding Doudna’s lab with a five-year grant to create the Center for Genome Editing and Recording as part of the Center of Excellence in Genomic Science (CEGS) program. The purpose of the Center is to improve CRISPR technology and implement robust readout technologies to assess natural gene variations quickly and accurately.
Here are some highlights from the AMA session:
Q: I recently read an article about a study published [DOI: https://doi.org/10.1101/243345] explaining that some people have an immune system primed against CRISPR, making any potential CRISPR treatments ineffective for them. What are some ways researchers could get around this to treat genetic disorders in people “immune” to CRISPR?
Lu Wang, Program Director in the Division of Genome Sciences at NHGRI: An immune response is the human body’s defensive reaction that recognizes an invading substance (antigen) and produces an antibody specific against that antigen. Examples of antigens include viruses, fungi, bacteria, or transplanted organs. An antibody can tag an antigen for attack by other parts of the immune system, or can neutralize its target directly.
CRISPR are DNA sequences in bacteria containing bits of DNA from viruses that have attacked the bacterium. Bacteria recognize these bits in DNA from similar viruses during subsequent attacks. Cas proteins, including the various versions of Cas9, are enzymes that chop up the recognized DNA of a foreign invader. CRISPR/Cas form the basis of the CRISPR/CAS technology that can specifically change genes within organisms.
The Cas9 enzymes often used for research are originally from common bacteria that can live in the human body that may have already formed immune responses against those proteins. Modifications of the CAS enzymes or finding different enzyme from microorganisms that do not cultivate in human bodies are among the ways to get around this challenge.
Q: What would you say is the most misunderstood thing about CRISPR that can cause people to be opposed to your research?
Carolyn Hutter, acting Division Director in the Division of Genome Sciences at NHGRI: I think a major misunderstanding is that CRISPR is equivalent to germline editing in humans, and that all work in this area should be opposed because of concerns related to genetic modification in humans. In fact, the vast majority of proposed applications of CRISPR are in basic research, as well as applications in plants, bacteria, and non-human animals. Further, a major focus of human applications are on somatic (non-inheritable) editing. A broader understanding of the potential benefits, risks, and applications of CRISPR would likely lessen some of the opposition.
Q: What barriers exist that might keep CRISPR from being more widely used once it is completed?
Kevin Doxzen, Science Communications Specialist at the Innovative Genomics Institute: I think that the most significant barrier is the health insurance system. Many of the therapeutic applications will cost hundreds of thousands of dollars. We hope that health care systems will evolve to make this technology available to those in need.
Q: What are your thoughts on the concept of "Designer Babies", and how CRISPR may lead to humanity customizing their children genetically? Should people use this technology to make their children "genetically superior", as in changing genes to maximize their child's mental/physical potential, or should it only be used for removing genetic diseases?
Christine He, a postdoc in the Doudna lab: With human trials for CRISPR-Cas editing already occurring, it is natural to wonder if the technology can be used to enhance desirable traits in humans. However, there are two important factors to keep in mind. First, the genetic basis for many physical attributes is not well understood. For example, variation in human height--a trait that you might guess would be determined by a single or a few genes--is actually influenced by thousands of genes. CRISPR-Cas can be utilized to target a very specific sequence in a gene, but manipulating a complicated network of genes to produce a desired phenotype is far less straightforward. The second factor to consider is that many traits you might associate with “designer babies”—such as high IQ or athletic ability—are likely determined by both heritable genetic factors and environmental factors. Even if we were able to edit the genome with exact precision and efficiency, the influence of environmental factors cannot be discounted.
Q: The litigation surrounding the patenting of CRISPR/Cas9 has been drawn out and quite vicious [see Bio-IT World’s coverage of the litigation here]. That's somewhat understandable given the potential of the technology (and its potential valuation). How has the battle over intellectual property affected the research your lab does?
Jennifer Doudna: The patent fight is unfortunate, but I’m grateful that it has not affected my lab’s research. We are working on fundamental aspects of CRISPR biology and technology, and we’re also partnering with various academic teams to move our developments into the clinic and into use for agricultural applications. As a scientist I try to stay focused on the things I can control, like our research directions and training my students, and leave the legal wranglings to the lawyers!
Q: Everyone likes to speculate on the enormous potential of CRISPR for the treatment of genetic disease, however we're not there and there will be more hurdles just like with any other pharmaceutical development. Based on your knowledge of the area, how far off are we looking? Is the promise of CRISPR more like solar panels (improvements are real and on the way) or nuclear fusion (It's been 20 years off for the last 50 years.)
Meredith Triplet, Project Coordinator at Doudna Lab: There are several aspects to be considered when thinking about the timeline of clinical applications of CRISPR. First, a disease needs to be well-mapped; scientists have to know which gene was mutated to cause the disease. Secondly, CRISPR is best designed to treat monogenic mutations (where there is only one mutation, not several). Thirdly, there is an issue of drug delivery: how is the CRISPR system going to get to the tissues that are impacted by the mutation? Fourthly, there are still some issues of off-target effects and efficiency of mutation. Finally, the process to ensure that a new drug is safe for general use is lengthy, and requires years of clinical trials. For diseases where the current mutation is understood, I expect clinical applications to appear in 5-20 years. Beyond that, I expect CRISPR technologies to be applied to more and more diseases.