CRISPR’s New Technique and Transthyretin Amyloidosis


CRISPR (clustered regularly interspaced short palindromic repeats) was discovered over a decade ago by Emmanuelle Charpentier and Jennifer Doudna, two scientists who recently shared the Nobel Prize. Scientists using genome editing (also called gene editing) are able to change an organism’s DNA.

According to a recent article in Popular Science, although gene editing techniques were first used in the 1900s, the new technology is more user-friendly and less expensive.

Scientists working in labs around the world have been using CRISPR’s DNA-editing technology to investigate possible treatments for many varied and complex diseases. The technology mimics scissors and cuts the DNA in a specific place. Then the scientists may remove, replace, or add the DNA at the spot where it was cut.

The Cas 9 Protein’s Effect on Invading Viruses

Cas 9 (CRISPR associated) cuts the genetic material from invading viruses. The scientists, Charpentier and Doudna, found that by altering the biological ‘guide’ used by the Cas 9 protein, they could select a specific site in the DNA where they wanted to cut. By using that process, new genes could be inserted or others could be deactivated.

Will the Benefits Outweigh the Risks?

Until now CRISPR’s gene-editing technology has been carried out in labs outside of the body. The defective disease-causing cells are removed from the body and the CRISPR technology is applied to the faulty cells which are then reinserted into the body.

Recently experiments are being conducted which are being called “one-shot”. The DNA editing technique is injected into the bloodstream directly. Diseases can now be treated easily and with less cost.

Yet this new technique carries some risk. It is possible to inadvertently edit healthy genes. This is called ‘off-target’. The technique can, in error, edit sequences that are somewhat identical but are not the actual faulty genes.

A Study of CRISPR and Transthyretin Amyloidosis

A small study involving six people was conducted recently to treat the six participants who have a rare genetic disorder named transthyretin amyloidosis. In this instance, CRISPR was delivered into cells of the liver. The study was published in the NEJM.

This small study follows an earlier trial investigating NTLA-2001. The NTLA clinical trial packaged CRISPR technology in a lipid nanoparticle. These transporters carry CRISPR’s gene-editing technology to the liver where transthyretin is produced.

Then CRISPR begins to correct the cells that are defective until the liver begins producing the true version of transthyretin.

In order to avoid off-targeting during the study, the researchers employed the use of a computer program that identified at-risk areas that might be incorrectly targeted by CRISPR.

When samples of these human liver cells were examined in the lab, the researchers were relieved to see that there were no off-target effects.

The New Study’s Primary Goal

Study participants were separated into two cohorts with each group receiving either a high dose or a low dose of CRISPR lipid nanoparticles. The group receiving the low dose averaged a fifty percent decrease in defective liver cells. The group receiving the high dose saw an average reduction of almost ninety percent.

Amyloid and Sickle Cell

Excess amyloid causes symptoms associated with sickle cell. Although the safety of the treatment was the primary goal of the new study, the investigators considered any reduction in symptoms an indication that the treatment is working. That is exactly what happened.

In most safety studies researchers continue testing higher doses to determine the most effective yet the safest level for patients. In this study, the researchers will monitor the patients for about two years post-treatment looking for genetic conditions or cancer. They will be especially alert to conditions that might be caused by unexpected gene changes which is one of the risks of CRISPR.

Controlling the Potential for Harm

One of CRISPR’s benefits is reaching most or even all cells. In this case, it is liver cells but it is potentially harmful. As a life sciences professor explained, a genetic mutation might inadvertently give instructions to cells that would cause them to divide and result in cancer.

Both solutions, editing inside or outside of the body, have drawbacks. Editing outside the body would mean that the researchers can edit the cells in the lab, but they cannot remove the liver to get to all the cells. Therefore they lose the advantage of not being able to detect rogue editing.

The disadvantage of editing cells inside the body leaves the researchers with no way of knowing if problems have occurred.

About Transthyretin Amyloidosis

Transthyretin amyloidosis is responsible for amyloid, a defective protein that accumulates in the body causing progressive nerve damage and potential heart failure. Symptoms may begin when a person is in their early twenties and may be fatal within seven to twelve years.

Looking Forward

It is difficult to tell at this juncture just what CRISPR will look like in the future. Scientists have been investigating new uses for CRISPR now for over a decade.

  • In 2019 a woman with sickle cell disease was treated with CRISPR; the results so far indicate that the treatment was successful
  • In 2021 CRISPR was injected into the eye of a patient to test a treatment for a disease that causes blindness.
  • An HIV treatment also appeared to be successful when tested on an animal model; it has yet to be tested on humans
  • Immunotherapy treatments that use CRISPR to modify immune cells are being tested to increase their potency against cancer.

There is no doubt that CRISPR has the potential to cure many human diseases.  One month ago, for the first time CRISPR edited cells in the human body. There are drawbacks, of course, but can they be overcome?

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Rose Duesterwald                                       October 27, 2021



Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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