Casgevy – BioQuakes

An article published in December of 2023 through ScienceNews identifies how the first CRISPR therapy approved in the U.S. will treat sickle cell disease. CRISPR therapy involves the process of changing the nucleotide sequence of a small segment of guide RNA in order to allow accurate targeting of almost any desired genomic locus for the purpose of correcting disease-causing mutations or silencing genes associated with disease onset (source). On December 8 of last year, the U.S. Food and Drug Administration approved gene editing, or CRISPR, therapy for use in patients ages 12 and older. The treatment, named Casgevy, is the worlds first treatment to alter cells using the Nobel Prize-winning molecular scissors. In addition, Lyfgenia, another gene therapy for sickle cell disease was approved on December 8.

Previously, patients relied on drugs such as hydroxyurea or bone marrow transplants which didn’t always work for everyone. Casgevy on the other hand relies on a patients own cells. CRISPR treatment alters the genetic blueprint of bone marrow cells that give rise to blood cells in order to make new healthy cells.

Approximately 100,000 people in the United States, most of them black or Latino, have sickle cell disease. Sickle cell disease is caused by a genetic defect in hemoglobin, the oxygen-carrying protein in red blood cells. While typical blood cell are flexible enough to slip through blood vessels, sickled blood cells are inflexible and often get stuck resulting in restrictions to blood flow and debilitating pain. People with severe forms of the disease may be hospitalized multiple times a year.

Many scientists are excited about this new treatment option. Kerry Morrone, a pediatric hematologist at Albert Einstein College of Medicine in New York City says CRISPR-therapy treatment for sickle cell disease can give patients a “new lease on life” commenting on the fact that people with the disease often miss school, work, or special events due to the excruciating pain.

Several clinical trials have tested the CRISPR based treatment Casgevy on participants. Victoria Gray, the first sickle cell patient to enroll in the trial recounted how the treatment changed her life. Gray had preciously described bouts of pain that felt like being struck by lightning and getting hit by a train at the same time. Now, pain-free, she is able to enjoy time with her family. Furthermore, Jimi Olaghere, another patient in the trial, told a similar tale. He says before treatment “sickle cell disease dominated every facet of my life” and “hospital admissions were so regular that they even had a bed reserved for me.” After the trial, he is pain free and able to present for his children while also doing the things he loves.

Of course with any new discovery, there are challenges. Patients who wish to be treated with Casgevy must first receive chemotherapy to wipe out existing bone marrow cells so the new ones have a chance to thrive. Chemotherapy can raise the risk of blood cancer and cause infertility. It also kills immune cells which puts patients at higher risk of dying from infections. In addition, the therapy may cost up to $2 million per patient, but healthcare costs for sickle cell patients are already high over their lifetime.

An article published the same day goes into more detail on how exactly this new treatment functions. The article states that the treatment also called exa-cel directs CRISPR to a gene, called BCL11A that typically prevents the body from making a form of hemoglobin found only in fetuses. The new therapy allows physicians to remove a person’s own bone marrow stem cells, edit them with exa-cel, destroy the rest of the person’s untreated bone marrow, and then re infuse the edited cells.

A second article published in January of this year goes into detail about the CRISPR system itself and how it can be used to treat many different conditions. The article states that CRISPR gene editing unlocks the ability to precisely target and edit specific genetic mutations that drive the growth and spread of tumors as well as new possibilities for the development of more effective and personalized cancer treatments. CRISPR gene editing is not only useful for the treatment of sickle cell disease, but also useful in the treatment of a much wider scale.

Similar to the methods in which CRISPR alters genes, in AP Biology class, we preformed a transformation lab in which we altered bacteria membranes through a heat shock in order to allow the plasmid, pGLO, to pass through the membrane and activate the gene for glow. CRISPR functions similarly to pGLO as they both are able to alter the genes inside of cells or bacteria in order to cure diseases or just make bacteria glow green as it did in AP Biology class.

I hope this article helped simplify the ways in which CRISPR therapy works to treat sickle cell disease and other major diseases as well as explaining how this new discovery opens of many new possibilities in the world of medicine and pharmaceutical development. I look forward to seeing where CRISPR gene editing and therapy goes and how many diseases it will be able to cure in the future. What do you think?

A blood smear of someone with sickle cell disease under a microscope

Scientists are starting to use genetic editing tools to edit out genetic diseases, starting with sickle cell disease.

Sickle cell disease is a non-dominant genetic disease that is the result of the red blood cells becoming well, sickle shaped. These cells then die early, and catch on things in veins, resulting in clots.

In addition, the cells aren’t able to properly deliver their cargo to cells- oxygen. The recipients then also promptly die early, resulting in a multitude of complications, many of which are potentially fatal.

CRISPR (short for “clustered regularly interspaced short palindromic repeats”) technology utilizes Cas9 proteins, guided with a sliver of RNA, and it will comb through the DNA and clip the matching strands off, in which it will either be forced to mutate, or function correctly (should it be a mutation that we are seeking to eliminate).

In this case, CRISPR is being used to alter the genes that cause this disorder (that without morality, natural selection would have done its work in weeding it out) as a replacement for the support (i.e. blood transfusions) .

Before the actual editing process, the patient’s stem cells are collected and the patient undergoes high dose chemotherapy to clear the existing bone marrow so that the edited cells can take prevalence

Casgevy, the name of one of the gene editing drugs, does exactly that. Blood is drawn, the blood is treated, then the now edited blood is reinserted into the patients bone marrow. It is currently approved for people 12 and over, but that is likely a base number and one’s doctor would properly evaluate for.

29 of 44 treated patients had achieved 12 consecutive months within the span of 24 months without SCD complications, and all 44 treated patients had successfully accepted the mutated stem.

Common side effects included low platelet and white blood cell levels, mouth sores, headaches, itching, febrile neutropenia, vomiting, abdominal pain, and musculoskeletal pain.

How many other genetic diseases can CRISPR edit out?

BioQuakes

AP Biology class blog for discussing current research in Biology

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