When CRISPR was introduced in 2012, it was viewed as a promising technology with potential applications in therapeutics in the far future. However, within a few years, CRISPR outgrew its predicted applications and escalated as a tool that is now synonymous with gene editing. As the number of CRISPR users and applications grow each year, CRISPR publications are increasing exponentially, and keeping track of the latest developments can get tedious. We have simplified this overwhelming process for you by reviewing the top 5 CRISPR achievements of 2017.
Using CRISPR to Excise HIV from Mice
HIV/AIDS-related diseases remain a major cause of deaths worldwide, and neutralizing HIV infections has been a longstanding issue in medical research for several decades. One of the reasons that HIV is so difficult to cure is that infection results in the viral genome being integrated into the human genome. This year, scientists made huge progress in this field by excising HIV DNA from genomes of live animals using the CRISPR/Cas system. The researchers introduced the CRISPR machinery in 3 animal models via adeno-associated viral vectors and observed 60-95% reduction in the expression of viral genes. This remarkable feat may serve as the basis of human clinical trials in the future.
Pigs Face the CRISPR Scissors
Two major studies reported modification of the pig genome using CRISPR. In one study, endogenous retroviral gene sequences, present in the pig genome from old infections, were successfully removed from the pig genome. Deleting these retroviral genes eliminates the possibility of the viruses infecting transplant recipients. These edited pigs survived in the lab without obvious health issues, providing hope for transplanting organs from pigs into humans in the future.
In another study, researchers introduced a gene that burns fat in mice into the pig genome. This reduced fat in pigs by 20%, thus allowing low-fat bacon in the future. Also, the modified pigs showed better resistance to cold, which is economically important as breeders often suffer losses of pigs due to deaths in freezing weather.
Scissors Turn to Pencils
While CRISPR/Cas9 is a powerful genome editing tool, the continued presence of Cas9 nuclease in the modified cells risked off-target effects. As several genetic disorders in humans are caused by point mutations, a tool that could replace a single base would suffice rather than the double stranded break created by Cas9.
A base editing system to change GC to AT was in place last year, using a naturally occurring enzyme. But changing AT to GC had not been achieved as no natural enzymes exist for the same. Researchers were working to develop such an enzyme and finally succeeded this year. The resulting enzymatic machinery was attached to a modified CRISPR system, wherein the guide RNA dictated specificity, while a dead Cas9 was used to avoid DNA cleavage.
In a parallel study, researchers used a catalytically-inactive Cas13 nuclease to edit bases in RNA, instead of DNA, to achieve a similar outcome. Transient nature of RNA allows temporary alteration of protein levels in the cell to study the downstream effects without permanently changing the genetic code.
These new tools resemble a pencil, as a single base pair is rewritten, as opposed to the conventional molecular scissors analogy.
Editing Human Embryos
Several complex animals have so far undergone genome editing. In the year 2017, however, human embryos were edited for the first time in the US using CRISPR. Researchers modified a gene responsible for thickening of the heart muscles by introducing the CRISPR machinery together with the sperm into the embryo.
Although these embryos were not implanted, this achievement was a major leap in gene therapy studies. As editing human genomes becomes more common in biomedical research, the scientific community will need to develop and enforce guidelines to ensure that the research is conducted ethically and responsibly. The National Academy of Sciences (NAS) and National Academy of Medicine (NAM) formed an advisory group this year to generate guidelines on human genome engineering.
Seeing is Believing
CRISPR has been used in countless applications based on the knowledge of its functioning. Yet, the exact process had not been visualized. Recently, researchers used atomic force microscopy to visualize the DNA cleavage by Cas9. This video is the first of its kind, revealing unknown details of the CRISPR/Cas9 cleavage process.
While the CRISPR innovations in 2017 were extremely exciting, we are looking forward to seeing the new ways that CRISPR will be used in the future. Will CRISPR be used for CAR-T cell engineering in patients? What new types of CRISPR enzymes will be developed? How will CRISPR impact personalized medicine and the biofuels and food industries?
Stay tuned to read our predictions for the CRISPR breakthroughs we will see in 2018!