In a groundbreaking medical achievement, researchers have successfully utilized CRISPR technology to rewrite the DNA of a baby suffering from a rare genetic disorder. KJ, a 10-month-old boy, became the first human ever to receive a tailored gene-editing therapy with CRISPR. He is currently fighting a chronic life-threatening condition called CPS1 deficiency. This serious condition affects about one in 1.3 million newborns and can result in life-threatening health problems.
After being diagnosed with CPS1 deficiency, KJ experienced serious health problems resulting from a mutation that caused his liver to malfunction. Conventional approaches, such as liver transplants, are insufficient. Only half of the infants impacted live long enough to get this procedure. Yet in that dark tunnel, the groundbreaking use of CRISPR base editing has offered a glimmering new ray of hope. This second-generation CRISPR tool acts like a spell checker, changing target DNA from one letter to another. This achieves gene editing in a much more targeted way than old school operations that slice and dice out the troublemaking genes.
The treatment has yielded promising results. Since undergoing therapy, KJ has adapted to a complete-protein diet. On top of that, he’s reduced his medication consumption by 50%! Medical experts view this groundbreaking treatment as a huge step forward for KJ. They say that it might be a game changer too in the fight against many other rare genetic diseases.
The Science Behind CRISPR Base Editing
Marco Herold, head of the Blood Cancer and Immunotherapy Lab at the Olivia Newton-John Cancer Research Institute, calls CRISPR base editing a “genetic engineering hack.” For one, he points to its innovative approach to changing genes. Base editing represents a radical new technique for gene editing. Unlike other CRISPR approaches, it edits the DNA with pinpoint precision without making cuts or breaks in the DNA strand. This precision is especially good news for diseases such as CPS1 deficiency, where whole mutations can be repaired with the least interruption.
KJ’s mutation was highly specific—it was only present in the liver. This organ is fundamental for detoxifying our bodies and producing important proteins. To get around this, the liver, as Professor John Rasko AO — head of the Centenary Institute’s Gene and Stem Cell Therapy Program — describes it, needs to function like a giant sieve. It detoxifies poisons and toxins, as well as producing hormones and proteins, which is why lipid nanoparticles carrying the new gene-editing products accumulate there. This focused approach has begun to reverse KJ’s disease, offering a glimpse into how other genetic therapies could cure other genetic disorders.
As exciting as KJ’s case is, experts warn that the promise of CRISPR technology cannot be applied across the board. As Professor Rasko notes, gene editing is a fundamentally different approach with strong quality control and rigorous regulatory approval needed to ensure that it is safe and efficacious. Every time we do something like this, we need to change the guide DNA. It is true that the technology itself must continue to mature. “It’s not just a one-size-fits-all.”
The Broader Impact on Rare Genetic Diseases
In Australia, an estimated 2 million of our population are considered to have a rare disease. Astoundingly, nearly 80% of these instances are rooted in genetics. Genetically, there are more than 5,000 such diseases recognized across the globe that have adversely affected the lives of millions. Although each is rare individually, these conditions represent a gigantic unmet medical need. “We have an unbelievably significant unmet medical need,” said Professor Rasko. Right now, there are FDA-approved treatments for only 5% of these rare genetic disorders.
If KJ’s therapy proves successful, it may lead to similar treatments for countless other patients who face the daily challenge of severe genetic disorders. “While KJ is just one patient, we hope he is the first of many to benefit from a methodology that can be scaled to fit an individual patient’s needs,” stated Rebecca Ahrens-Nicklas, a researcher involved in the project.
Experts claim that not every rare disease is appropriate for gene-editing modalities such as CRISPR. As they write in their report, they feel that hundreds, if not thousands of diseases are ripe for similar methodologies to be applied. Things get complicated in cases where there are many different mutations. “If you have multiple mutations … then it becomes difficult,” remarked Professor Herold.
Looking Ahead
Even as a furore grows over this transformative therapy, scientists continue their efforts to improve the approach and push the boundaries of what it can do. The road forward On the heels of economic headwinds, the focus now must turn to equitable access to these novel treatments. “To bridge that gap economically is the biggest hurdle,” Professor Herold said.
Still, in the face of these obstacles, the successful treatment of KJ still represents an extraordinary breakthrough in gene therapy and genetic engineering. Former FDA official and current Johns Hopkins professor Peter Marks called KJ’s therapy “transformational,” paving the way for one-time treatments in other rare genetic diseases. History of CRISPR The pioneers of CRISPR technology won the 2020 Nobel Prize for their innovative research. It is a phenomenal recognition of their scientific breakthrough!
