Many powerful discoveries arise in unexpected places; CRISPR is a gene editing system that was first discovered in the DNA of bacteria in the 1990s by Dr. Francisco Mojica in Spain. CRISPR is now being tested to fight bacterial antibiotic resistance, among many other applications.
What is CRISPR?
CRISPR is the name given to a cluster of unusual DNA sequences in the immune systems of bacteria that are able to select and cut specific sections of DNA. The CRSPR clusters in the bacteria recognize the DNA of viruses that have previously been present and cut them up in self-defense.
CRISPR (clustered regularly interspaced short palindromic repeats) has two components; an enzyme called Cas9 that acts as a genetic scalpel and an RNA guide or homing device that leads the scalpel component to the correct string of nucleotides. With these two parts, CRSPR technology can be used by humans to locate and change specific genes. Michael Spector of The New Yorker explains that researchers have created programmable and “synthetic versions of the RNA guides” and have been using them with the Cas9 scalpel enzyme since 2012-2013. The early studies have been primarily carried out on DNA samples, plants, worms, and mice in order to practice selecting, changing, deleting, and replacing genes. Two of the leading scientists in this developing field are Dr. Feng Zhang and Dr. Jennifer Doudna.
CRISPR is groundbreaking because it’s faster, cheaper, and more accurate than previous gene editing technologies including TALENS and zinc-finger nucleases. CRISPR has many possible applications, including treating disease, increasing crops’ nutritional value, and even changing the organ donor landscape by tackling the persistent retrovirus risk associated with using pig organs. Mice have been bred with the Cas9 (genetic scalpel) component integrated into their permanent genome which allows scientists to add the RNA guide component and carry out multiple probes and genetic studies at once. Because many diseases involve multiple genes, being able to target multiple genes or “multiplex” with CRISPR may be very useful. As with much genetic manipulation research, CRISPR studies have great potential and are also controversial.
Dr. Lu and CRISPR: Taking on Antibiotic Resistant Bacteria
Dr. Timothy K. Lu and a team of MIT researchers are using this CRISPR gene editing technology in an effort to address and essentially turn off dangerous bacteria’s antibiotic resistance. MRSA and many other types of harmful bacteria develop and hold antibiotic resistance in their genes. Lu and his colleagues are aiming to change that.
They have already used CRISPR to attack the bacterial genes that destroy antibiotics drugs as well as those that enable bacteria to cause disease at all. They have developed two methods for delivering the CRISPR: using bacterial viruses called phages as transports and, as Loren Grush of Popular Science reports, “leverag[ing] the bacteria against one another.” This refers to the fact that bacteria pass genes between themselves and so will share CRISPR genes. This is the slower of the two methods.
Lu’s team has found that CRISPR can be used to remove bacteria’s antibiotic resistant genes and so boost the effectiveness of existing drugs. Also in Popular Science, he says that this method’s adaptability is of great benefit: “when a new gene comes out that’s bad, we can go and design a new version of the system that can counter that.”
Lu and his team’s 2014 study was published in the journal, Nature Biotechnology, and in test tubes they killed more than 99 percent of the bacteria’s genes that destroy antibiotics. You can follow Dr. Lu’s work on the Synthetic Biology Group's website.
CRISPR and Human DNA
Using CRISPR with human DNA is a much-debated process. Unviable human embryos (physically incapable of developing) were used in China in 2015 to test the CRISPR gene editing process. The New Yorker reports that less than half of the embryos tested were successful; the CRISPR made unintended cuts and substitutions and the embryos did not usually retain the inserted DNA. Donated IVF embryos which are terminated after one week are being used for research in Britain in 2016. In September of 2016, NPR shared that Swedish scientist Fredrik Lanner is attempting to use CRISPR to edit the DNA of donated healthy human embryos, which will be destroyed after a maximum of two weeks. He is doing this as a means of studying embryonic development and in hopes of treating infertility and possibly other diseases and reducing miscarriage risks. NPR explains that critics worry about “designer babies” or that, “[m]aking changes to the DNA in human embryos could accidentally introduce an error into the human gene pool, inadvertently creating a new disease that would be passed down for generations.”
In December of 2015 an International Summit on Human Gene Editing was held in Washington, D.C and stated that “it would be irresponsible” to carry out germline editing at this point (germline editing describes genetic changes that would be passed down throughout the gene pool and impact future generations) but that it should be revisited in the future. They point out the need for an ongoing forum, and that “[t]he international community should strive to establish norms concerning acceptable uses of human germline editing and to harmonize regulations.” They also stated that unviable embryos and human cells that would not be passed on should be used “subject to appropriate legal and ethical rules and oversight.” The Human Gene Editing summit report is available on The National Academies of Sciences, Engineering, and Medicine website.
In June, 2016, the National Institute of Health made a historic decision when they approved a proposal for scientists at the University of Pennsylvania to carry out a CRISPR trial in which they will gene edit the immune cells of people with cancer and then infuse the edited cells back into the patients. Shelly Fan of Singularity Hub reports that the goal is for the immune cells to be changed in several ways, so that they recognize and attack cancer cells more effectively and to better withstand cancer’s efforts to shut them down. Michael Le Page of New Scientist reports that because the process is imperfect, “the T-cells put back into the patients will actually be a mix of cells with various combinations of these changes.” The same Singularity Hub article reports that “the proposal still has to pass the scrutiny of the FDA and the institution’s ethics boards.”
-by Julia Travers