Crispr is no longer a buzzword. According to a recent article in The Guardian, it has become the ‘molecular scissors’ that will enable scientists to rewrite our genes or as often said, “rewrite the book of life”. It also carries a host of ethical questions that must be addressed.
Of course, creating designer babies will always grab headlines, but that is not what CRISPR (crisper) is about. It is about gene editing. It is about the trials that are being conducted to evaluate treatment for many different diseases.
The list includes complicated disorders as cancer or sickle-cell anemia. CRISPR promises to treat diseases that are the result of genetic mutations. And these include muscular dystrophy as well as congenital blindness.
About Gene Editing
In 2020, the award of the Nobel prize to Jennifer Doudna, biochemist, and Jennifer Doudna, microbiologist, caused a great deal of excitement in the medical community.
The team had developed CRISPR-Cas9, a gene-editing technique. As of this writing, Crispr therapies are already being evaluated in human trials. Dr. Doudna, Professor of Chemistry and of Molecular and Cell Biology at the Department of Chemistry and Chemical Engineering at the University of California, said that she was impressed at the speed with which Crispr’s research has progressed.
Diabetes, heart conditions, and Alzheimer’s have one commonality. The disorders are caused in part by genes. People are vulnerable when they inherit the wrong modified (variant) gene.
The Birth of Gene Editing
Scientists have been attempting gene editing since 1970 with the goal of treating patients through gene therapy. However, the genetic component has been complicated because there are so many genes involved.
For example, one gene would have to be identified out of 21,000 genes in the DNA of each cell. Accurate tools are required in order to locate the gene, snip the DNA at the exact point and finally replace the errant gene with the new one or perhaps a portion of a gene.
But there are certain diseases, e.g. cystic fibrosis, that may be caused if only one or even several genes are malfunctioning. Cystic fibrosis is an excellent example of a disease that may be cured through gene editing. It requires the replacement of malfunctioning genes with normal, healthy variants.
Although biologists have been editing genes for years, the edits have not been precise and therefore were not safe for clinical use.
If in the editing process other genes are altered, the consequences can be serious enough to cause cancer.
CRISPR-Cas9’s Effect on Gene Editing
Crispr’s gene-editing technique uses Cas9, an enzyme molecule that was initially found in bacteria. It can be programmed to locate a target. Crispr carries RNA, a genetic material somewhat like DNA, which carries the sequence (genetic information) at the target location.
Note that a “sequence” gives the scientist genetic information that is located in a certain DNA segment.
Once the enzyme locates the DNA sequence and it matches the RNA strand, it snips the DNA double helix in half. Other enzymes are then able to put an additional piece of DNA (the healthy sequence) in the break.
Professor Doudna explained that the rationale is to begin their efforts by working with one gene in a tissue or cell which would be an easy target. The researchers intend to prioritize disorders for which there are no current treatments. Sickle-cell anemia comes under this heading.
CRISPR-Cas9’s First Treatment
A year ago, sickle-cell patient Victoria Gray of Mississippi was treated at a hospital in Tennessee using the experimental Crispr therapy developed by researchers at the hospital.
Stem cells from her bone marrow were removed, engineered, and transfused back into her body.
To date, Victoria has not experienced her usual symptoms such as trips to the hospital for blood transfusions or even the pain that she endured for so many years.
Victoria is currently participating in new Crispr trials in Boston for beta-thalassemia and sickle-cell disease. The trials are being conducted by Vertex Pharmaceuticals in partnership with Crispr Therapeutics.
About Crispr Delivery Challenges
Berkeley bioengineer Niren Murthy explained that it is easy to get Crispr into the bloodstream when treating leukemia. However, when working with other tissues, size becomes a major drawback. The drug must cross the barrier that separates the bloodstream from the tissue’s cells.
The obvious solution to solve the transportation problem is to put the active ingredients into a small vehicle (vector) such as a harmless virus. In fact, this is the process used to deliver the active ingredients for the Covid vaccines.
But again, the size of the components of the CRISPR system is still too large to penetrate the membranes and get into the tissues.
Treating Childhood Blindness
Editas and Allergan are conducting a trial using Crispr to treat an inherited type of childhood blindness which is called LCA10. The treatment is administered by injecting Crispr that is transported within a virus into the eye.
The researchers believe that the unique characteristics of the eye may prevent the most common side effects.
Professor Murthy is currently researching a Crispr treatment for a severe form of Duchenne muscular dystrophy (DMD). Mutations in a dystrophin-producing gene cause DMD. Symptoms of DMD are loss of muscle fibers eventually resulting in death.
Considering that brain tissue can be edited easier than muscle, Professor Murthy believes that Crispr therapy will be widely used for neurological genetic conditions.
Professor Murthy acknowledges that it may take about five to ten years for Crispr therapy to see major clinical use.
Professor Doudna, on the other hand, expressed amazement at the speed with which Crispr has been accepted by scientists worldwide.
