Clustered Regularly Interspaced Short Palindromic Repeats is more commonly known as CRISPR. As reported recently in Science News, the CRISPR/Cas9 “molecular scissors” is slated to make its highly anticipated debut in first-ever human clinical trials.
Lacking a specific gene can make a patient more susceptible to disease. Perhaps one of the main reasons CRISPR holds such promise is the ease with which it can edit a gene.
In one of the three trials, the gene editor will be injected into the patient’s eyes; then it will snip out a mutation that causes a form of blindness.
A Promise Held Since 2012
CRISPR made its debut in 2012 with promises of a brighter future for patients with genetic diseases.
The CRISPR gene editor is initially focusing on blood disorders, blindness, and cancer. The success of these trials could eventually lead to therapies for almost ten thousand diseases that are caused by mutations.
Down syndrome or sickle cell anemia are examples of the disease scientists are waiting to cure.
About the Protocol
CRISPR can be approached in two ways. One method is ex vivo gene editing. Human cells are extracted, engineered in the lab then reinjected.
The second approach, in vivo gene editing, involves delivering CRISPR-Cas9 into the body where it edits the DNA from a point within the cells. CRISPR delivery may possibly be in nanoparticles or even encoded within the DNA. If successful, then it can be removed from the body.
CRISPR/Cas9 can be called a re-engineered “virus-hunter”, cutting DNA at certain locations. RNA, similar to the DNA genetic molecule, is the CRISPR. It guides the Cas9 enzyme to certain places in the genome.
The cuts are made into the DNA and can either remove the errant parts of the DNA, disable genes or make needed repairs.
About the First Two Trials
Since this is the first time that CRISPR gene editing is being used on humans, the emphasis will be on safety and efficacy.
In the first two trials, the scientists will use CRISPR/Cas9 to remove several human cells, edit the DNA, then return the cells back into the patient by injection. The edited cells will now be ready to combat disease.
About the Third Trial
In the third trial, CRISPR/Cas9 will be working with patients who have a form of inherited blindness called Leber congenital amaurosis. Severe dystrophy of the retina usually occurs soon after birth.
In July 2019 two companies, Editas and Allergan initiated recruiting for the Leber gene-editing trial. In this trial, the molecular scissors will be injected into the patient’s eyes.
Two guide RNAs will direct Cas9 to the proper location and then cut two pieces of the gene mutation.
The disease is caused by a gene mutation in the CEP290 gene that leads to a nonfunctional protein. The protein is the root cause of the disorder. The paradigm continues with the death of rod cells that are situated in the retina. Blindness results when light-gathering photoreceptors cannot renew themselves.
The First Participants
In testing for safety, CRISPR will be injected under the retina in small amounts. New volunteers would receive higher doses if the tests prove to be safe. A member of the research team stated that they intend to work with the most serious cases first. Children would be tested at a later date.
An Ethical Hurdle
CRISPR’s reputation incurred a temporary setback a year ago when a scientist in China edited embryos that produced twin baby girls. This alarmed the entire scientific community and it immediately called for more regulation.
Reassurances were given by one of the bioethicists that if the errant gene is repaired rather than replaced, there will be no inherited changes in DNA. Additional information about this subject is available here.
A Major Step into the Unknown
It is not known as yet whether or if CRISPR will work in the human body. However, scientists have already made statements to the effect that even if these initial trials were to fail, the quest to perfect CRISPR will continue.