CRISPR

CRISPR

I am so ancient, I don’t even buy green bananas, but there is hope – read on!

You may not have heard of CRISPR (pronounced ‘crisper’, an acronym for “Clusters of Regularly Interspaced Short Palindromic Repeats”) but scientists can now edit genes in plants, animals and humans. With CRISPR, they can make these edits quickly and cheaply.

Specialists cut and replace or edit a patient’s DNA to repair hereditary defects or damaged DNA. CRISPR is like software programming for DNA. Eventually, CRISPR will help cure all human disease of genetic origin.

There are two different gene therapies. Germline changes DNA in reproductive cells (like sperm and eggs) which is passed down from generation to generation. Somatic therapies target non reproductive cells and this affects only the recipient. I am trying to find out where in the body the editing is done and how the change is transmitted to every body cell. Google not helping. If you know, please post your answer in ‘Comments’.

Gene editing can also improve any living organism such as animals and plants in agriculture for more yield, nutrition, etc. It may eradicate malaria by changing the DNA in mosquitoes. (Eradicating nasty humans a possibility?)

CRISPR is now being used on humans in the US. Researchers are taking immune cells from the patients’ own bodies and editing them with CRISPR before putting them back. The hope is that these edited cells will be better at identifying and attacking cancer, for instance.

Sickle Cell Anemia

Sickle cell anemia, can damage nerves and organs, including kidneys, liver and spleen. It can be fatal. However in June 2020, after receiving CRISPR treatment, a sickle cell patient lost “virtually all the complications of her disorder.”

Thalassemia

CRISPR treatment has had similar long term success with thalassemia which can cause bone deformities in the face and skull. People who have thalassemia may also have severe osteoporosis (brittle bones). Too much iron in their blood. This can cause damage to the heart, liver, or endocrine system (glands in the body that make hormones, like the thyroid gland and adrenal glands). A US patient with the disease was treated and within five months was able to stop receiving blood transfusions.

Genetic Disease

There are more than 6,000 diseases caused by genetic mutations and 95% of them have no approved therapy or treatment.

More than one million babies in USA are born with a chromosomal abnormality each year. More than five million babies are born with a genetic disease or major birth defect each year. Birth defects or genetic conditions cause more than 20% of infant deaths. About 10% of adults in hospitals are there due to genetically related problems. About 30% of children in hospitals are there for the same reason. CRISPR technology has the potential to solve all these problems permanently.

A company called Verve has demonstrated it was able to “knock out” two genes in monkeys associated with “bad” (LDL) cholesterol. As a result, the monkeys’ LDL cholesterol levels fell as much as 60%. And their triglycerides level plunged as much as 65%.

As we know, bad LDL cholesterol and high triglycerides each increase the risk of heart disease and stroke. This research shows that Verve’s base editing therapy may dramatically reduce these health risks. And there were no serious adverse effects. The therapy was safe and well tolerated by the monkeys and the two genes targeted in monkeys are also present in humans. That means there’s a good chance Verve’s therapy will work well in humans also.

Mitochondria

CRISPR-CasΦ (see video above) is the smallest CRISPR enzyme identified to date. That’s important because its compact size will make the CasΦ more effective at entering cells to make the desired genetic edits. By researching bacterial toxins, scientists at the Broad Institute of MIT and Harvard just discovered a CRISPR enzyme that can enter mitochondria. This is a first. All prior enzymes, are too large to get into mitochondria. That’s made it impossible to pursue therapies to address diseases and conditions caused by faulty mitochondria.

Why is this important? Mitochondria are the cells’ power plant. They are inside every cell, and their job is to turn oxygen and nutrients into energy. Each cell is wholly dependent on the mitochondria. If they aren’t functioning properly, the cell dies. That’s when mitochondrial diseases occur. Mitochondrial diseases can be severe. In extreme cases, damaged mitochondria can lead to heart failure, dementia, or seizures.

Up to this point, scientists have not had a tool to address mitochondrial diseases. That’s been the last frontier in genetic editing. And that’s why this breakthrough is exciting. The team at the Broad Institute has filed patents on what it calls a mitochondrial base editor.

I will release new blogs on CRISPR as the technology develops.

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