Gene editing has a banner year in 2023

It shouldn’t have been surprising at all. Perhaps no technology has more power to transform medicine, and its great potential is just beginning to be realized. Gene editing can be used to remove, insert, or change parts of our genetic code. We’ve been able to edit DNA for years, but new technologies like CRISPR mean we can do it faster, more precisely, and more efficiently than ever before. In 2023, we will see the first approval of a CRISPR-based gene-editing therapy. And more to come. So let’s take a look at the developments that made the news this year. What is the promise of gene editing, and what are the current pitfalls?

Lucky break and next steps

Casgevy, the first CRISPR therapy, has been approved in the UK and US to treat sickle-cell disease. And it is on the cusp of approval by the European Union. Sickle-cell disease is caused by a mutation in the hemoglobin gene that leads to a characteristic crescent moon shape in red blood cells. Treatment does not address the underlying cause of the disease; instead, it interferes with another gene, one that blocks the production of a type of hemoglobin that humans normally produce only in the womb and during infancy. With that gene out of commission, the production of this second type of hemoglobin continues. The therapy works because cells containing fetal hemoglobin do not form sickles. You can read more about the fascinating backstory of Casgevy’s development in this story by my colleague Antonio Regalado.

Why go at it in this roundabout way? Newer versions of CRISPR work best as a pair of scissors, creating snips that suppress genes. That limits its usefulness. New versions of CRISPR will allow researchers to change the genetic code or even insert new genes, which will make it possible to solve different types of genetic diseases.

Verve Therapeutics, for example, is testing a method called base editing. Jessica Hamzelou covered this technique in depth in this January story: There are four bases in DNA: A, T, C, and G. Instead of cutting DNA, the CRISPR 2.0 machinery is able to convert a base letter to another. Base editing can swap out a C for a T, or an A for a G. According to Kiran Musunuru, co-founder and senior scientific advisor at Verve, It no longer works as with scissors, but especially with a pencil and eraser.

The Verves therapy, which is currently being tested in a small clinical trial, replaces a base in a gene for a protein called PCSK9, which is linked to high cholesterol. (The therapy is one of the MIT Technology Reviews 10 Breakthrough Technologies 2023.) That change suppresses the gene, which means the body makes less PCSK9 and cholesterol levels fall. In November the company announced interim results: an injection of the therapy reduced the level of LDL in the blood by up to 55% in 10 people with a genetic condition that causes high cholesterol.

CRISPR 3.0, which allows scientists to replace pieces of DNA or insert new bits of genetic code, is still being tested on animals. One company, Prime Medicine, plans to seek FDA approval to launch human trials of a treatment for chronic granulomatous disease, a genetic immune disorder, in 2024.

The traps remain, at least for now.

The only approved CRISPR therapy is not a simple fix. Patients must undergo a bone-marrow transplant: after chemotherapy to destroy their defective cells, the stem cells are removed, edited in the lab, and then reinfused. Jimi Olaghere, one of the few people who received the therapy, wrote about how difficult it was. The process of collecting the cells left him so weak that he needed blood transfusions. And chemo means dealing with nausea, weakness, hair loss, debilitating mouth sores, and the risk of worsening the underlying condition. All told, he spent 17 weeks in the hospital.

Due to the complexity of the treatment, you won’t be surprised to know that it costs an estimated $2.2 million. That price tag means it’s out of reach for many, especially people in low-income countries.

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