CRISPR cas9 based gene therapy promise to revolutionize the medicines including the treatment of genetic disorders. The diseases that once were considered unsolvable and incurable.
The CRISPR system primarily derived from bacteria where it evolved to cut and then stored foreign particle (usually viruses). Later, the scientists honed this system and utilized as a gene editing tool in 2012.
Now, with the CRISPR technology, we can edit or delete any DNA target more precisely than ever before. The researchers develop CRISPR mediated therapies that enable to modify and correct genetic error or mutations.
Explore more about CRISPR: What is CRISPR cas9?
These claims and expectations regarding CRISPR are now possible. And there are even some breakthroughs by using CRISPR on some of the following diseases.
Cancer could be one of the primary targets for CRISPR. As cancer caused when there is mutation occur in some specific genes. The CRISPR system can be developed in such a manner that it will only target and correct those mutated genes. And hence restore their normal function.
Currently, the CRISPR clinical trials are carried out in China, where it used in patients with advanced esophagus cancer. Both lung and esophageal tumor cells expressed PD-1 protein molecules on their surface that instruct the body’s natural immune system (T-cells) not to attack.
The researchers from the Hangzhou Cancer Hospital, China, used CRISPR technology to knocked out PD-1 receptors gene from the tumor cells. These genetically altered tumor cells are then reinfused into patient bloodstream. Hence, to enhance the T cells anti-tumor activity.
By using CRISPR to knocking out, PD-1 is an ideal way to treat other cancer types too. Edward Stadtmauer leads the first CRISPR clinical trial in the US at the University of Pennsylvania. They are using this same approach to treat multiple myeloma, melanoma, synovial sarcoma and myxoid/round cell liposarcoma.
Alzheimer’s is among those diseases for which there is no cure available. It is a neurodegenerative disease, which is fatal and gradually destroy memory and cognitive processes.
Today, Alzheimer effect 5.8 million Americans with vast majority over the age of 65.
Research has shown the genetics behind Alzheimer’s that involve both Risk and Deterministic genes that influence this disease. Soon, scientists may be able to target these genes specifically via CRISPR to treat Alzheimer.
Recently, CRISPR was able to identify new biomarkers involved in Alzheimer. This not only helps us in the early diagnosis but telling us progression level of it. And soon we may able to cure it altogether.
For the first time, Dr. Martin Ingelsson of Uppsala University, utilized the CRISPR technique to disrupt the amyloid precursor protein (APP) gene, involved in early-causing Alzheimer.
Moreover, Dr. Subhojit Roy of the University of Wisconsin-Madison, using CRISPR mediate strategy to change Alzheimer amyloid pathways. Thus, altering amyloid precursor protein (APP) proteins.
3. Cystic Fibrosis
Cystic fibrosis occurs because of mutations in a gene called Cystic Fibrosis Transmembrane Conductance Regulator or CFTR. During this disease, the body makes thick and sticky mucus, which causes severe respiratory problems.
Although there are new drugs like ivacaftor and lumacaftor available, which helps to prolong the life of a CF patient. However, still, there is no definite cure.
Research has shown that CRISPR could be used to cure Cystic fibrosis. CRISPR-based biotech companies like Editas Medicines and CRISPR Therapeutics are working to find treatment for such disorders.
Meanwhile, the problem is that there are several types of mutations in the CFTR gene. And sometimes mutations of one CF patient in the CFTR gene is different than the other one.
However, we can tailor CRISPR for every individual patient. Or develop different CRISPR therapies for different genetic mutations in the CFTR gene.
Currently, the Editas is with working with Cystic Fibrosis Foundation Therapeutics Inc. to develop CRISPR-based therapies for not only the most common mutations in the CF gene but also the rare ones.
4. Eye Borne Diseases
CRISPR can also target several eyes borne diseases such as Retinitis pigmentosa, retinal dystrophy, Leber Congenital Amaurosis and more.
Moreover, the eye is an immune-privilege part meaning they have a different immune system than the rest of the body. Even though it has an immune system which protects them from infections and also regulates healing processes. While eyes lack a vascular system, that makes its immune system different from the rest of the body.
CRISPR exploits this fact and can efficiently work in the eyes without been interrupted by the host immune system. Moreover, genetic blindness is because of various known mutations. That makes it easier for CRISPR cas9 system to target those mutations and correct them.
Recently, CRISPR-based biotech company – Editas medicines are working on using CRISPR for curing Leber Congenital Amaurosis. The firm has now been given permission by the US food and drug administration agency (FDA).
Similarly, Dr. Qin Liu of Harvard University is developing CRISPR mediated therapy to treat Retinitis pigmentosa. A genetic disorder caused by mutation P23H that leads to the break downing of cells in the retina. Dr. Qin using CRISPR Cas9 to knocking out P23H. They did so successfully in mice.
5. Duchene Muscular Dystrophy
A mutation causes Duchene muscular dystrophy in a gene called DMD gene that responsible for dystrophin protein that is vital for muscle contraction. DMD disease manifests gradually and slowly weakens and deteriorates muscles in the body.
As the Duchene Muscular Dystrophy is because of the mutations in the one single gene. That makes CRPSR Cas9 is an ideal candidate to treat it.
A team of researcher led by Dr. Eric Olson of the University of Texas trying to use CRISPR Cas9 to correct ‘Mutations hotspot’ region in the dystrophin gene. It means instead of fixing individual mutation, use CRISPR Cas9 to cut a whole ‘mutation prone’ area and that region is labeled as exon 51.
Their finding demonstrates that this method is fruitful in cell lines and mice. Moreover, recently, Dr. Eric co-founded company ‘Exonics Therapeutics’ put forward this method to treat Duchene muscular dystrophy in puppies’ models.
Boston-based biotech company Editas Medicines also follow CRISPR approach to treat Duchene Muscular Dystrophy.
CRISPR could be used in several ways against AIDS, by destroying HIV. Either by targeting the viral DNA inside the infected cells or by making the cells resistant to HIV.
Also, CRISPR was successfully used on rats in the controlled environment to remove the HIV-1 virus.
Some reports have shown that certain individuals are naturally immune to HIV infection, due to a mutation in a gene called CCR5. The gene encodes for a surface protein on immune cells that HIV uses to infect them. Through CRISPR, we can deliberately mutate the CCR5 gene to make it resistant. Currently, this is in early trial stages in animal models and cell lines.
Recently, a Chinese scientist, He Jiankui, successfully created first ever CRISPR edit Babies named Lulu and Nana. According to his claimed that both babies are HIV-1 resistant. He did so by using CRISPR gene editing technology to knock out the CCR5 gene.
7. Huntington’s Disease
Huntington’s disease is also a neurodegenerative disorder that involves the breakdown of nerve cells in the brain. It destroys a person both mental and physical abilities.
Mutations in a single gene cause this disease, and thus, make it a very effective target for CRISPR Cas9.
A team of researchers led by Dr. Beverly Davidson at the Children’s Hospital of Philadelphia used CRISPR and have successfully correct mutations in Huntington’s mice models. Thus, paving the way for future use in humans, and clinical trials.
Dr. Xiao-Jiang Li at Emory University followed a different approach by using CRISPR Cas9 to permanently suppresses the huntingtin protein expression from the mutated gene. Dr. Xiao did so successfully in mice.
8. Sickle Cell Disease
Sickle cell anemia is a blood disorder caused by a single base mutation in a beta-globin gene that encodes hemoglobin protein. The mutation changes the shape of the blood cells into sickle-like.
As a single change in a single gene cause this disorder, thus, make CRISPR an excellent candidate for treating it.
Vertex Pharmaceuticals licensed a new CRISPR/Cas9 based therapy – CTX001 aims to treat sickle cell anemia. The method involves the harvesting of blood cells from a sickle cell anemia patient. By utilizing the CRISPR – Cas9 gene editing approach to correct beta-globin mutation and re-implanted into the patient body. They are hence restoring the normal function of Hemoglobin. Successfully, the procedure achieved in mice having sickle cell diseases.
Moreover, Dr. Daniel Dever of Stanford University also used CRISPR cas9 approach to treat sickle cell disease. By using CRISPR, they first introduce DNA break in the ß-globin gene, followed by correcting it with homologous recombination.
β-thalassemia, like sickle cell anemia, is also a blood disease caused by a mutation in the same gene – ß-globin gene.
The above discussed, CTX001 therapy, developed by Vertex Pharmaceuticals could also be used as a cure for β-thalassemia. Similarly, Dr. Dever approach based on CRISPR and homologous recombination is another possible treatment for it.
Moreover, CRISPR therapeutics and its partner Vertex Pharmaceutical begin first CRISPR clinical trials in Europe to treat the patient with β-thalassemia.
10. Severe Combined Immunodeficiency (SCID)
SCID also was known as ‘Bubble Boy Syndrome’ is a rare and life threating genetic disorders developed by birth. Children with SCID have little or even no immune response to fight against invading bacteria or viruses and prevent infection. Usually, the patient body interferes with their immune system to perform their correct function.
A mutation causes SCID disease in either of these three genes IL2RG or JAK3 or ZAP70. The CRISPR-Cas9 system could be utilized to edit these mutated genes and correct SCID.
A team of researchers at the Department of Pediatrics, the University of Alabama at Birmingham used CRISPR/Cas9 approach to correct SCID causing mutations in one of their patients. The study involves the collection of skin/fibroblast cells followed by inducing with inducible pluripotent stem cell (iPS) technology. iPS cells are then treated with CRISPR Cas9 to correct JAK3 gene mutation.
Even though Aging is a natural process but it is also considered a disease. With Aging, the body gradually and slowly loses its functions and results in other complications such as Alzheimer’s and Parkinson diseases and more.
However, CRISPR Cas9 technology is also showing promises in slow downing aging and against age-related disorders.
Currently, a Harvard geneticist and a CRISPR pioneer Dr. George Church is working to slow and reverse aging by using CRISPR technology.
Moreover, a team of scientists at the University of Alabama, Birmingham used mice as a model and reversed skin wrinkle and hair loss.
Recently, a group of researchers at the Salk Institute developed a new CRISPR/Cas9 based therapy to suppress the aging mechanism in mice model with Hutchinson-Gilford progeria syndrome. Their research paper entitled “CRISPR/Cas9 therapy can suppress aging, enhance health and extend life span in mice”.
Video: The end of the genetic disease
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