In February 2025, doctors at Children’s Hospital of Philadelphia did something that had never been done before in the history of medicine. They took a six-month-old baby named KJ, who was born with a fatal genetic disease called CPS1 deficiency, and gave him a drug designed for one person on the entire planet. Him.
What Is CRISPR?
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. It’s a molecular tool that scientists borrowed from bacteria, which have been using this system for billions of years as a defense mechanism against viruses. In 2012, Jennifer Doudna and Emmanuelle Charpentier figured out how to reprogram this bacterial immune system to edit any DNA sequence — earning them the Nobel Prize in 2020.
Think of your DNA as a massive book, three billion letters long. Sometimes there’s a typo — a single wrong letter in the wrong place. CRISPR is like a molecular spell checker that can find that exact typo and fix it.
Three Breakthroughs That Changed Everything
1. The First Personalized Gene Therapy (Baby KJ)
Baby KJ was born with CPS1 deficiency — his body couldn’t process ammonia, a toxic byproduct of protein metabolism. Without treatment, ammonia would build up and cause brain damage or death. He was too young and too small for a liver transplant.
Researchers at Penn and CHOP sequenced KJ’s DNA, identified the exact mutation causing his disease, and built a custom CRISPR editor targeting his specific genetic typo. They packaged it in lipid nanoparticles and injected it. Within days, his ammonia levels stabilized. He went home.
A custom drug, for one patient, designed and manufactured in months.
2. Epigenetic Editing — No Cutting Required
Traditional CRISPR works by cutting DNA, which carries risks of unintended damage. A new approach called epigenetic editing doesn’t cut anything. Instead, it adds or removes tiny chemical tags (methyl groups) that control whether genes are turned on or off.
Think of it as the difference between cutting a page out of a book versus putting a sticky note over a paragraph. The text is still there, but the cell can’t read it. This is reversible, more precise, and potentially safer for conditions where you want to silence a gene rather than destroy it.
3. One Shot That Permanently Lowers Cholesterol
In November 2025, Verve Therapeutics published results of a clinical trial where a single CRISPR injection permanently lowered LDL cholesterol by editing the ANGPTL3 gene in liver cells. One shot. Not a daily pill. Not a monthly injection. One treatment, permanent effect.
The implications go beyond cholesterol — the same approach could target Lp(a) (a genetic risk factor for heart attacks that affects 1 in 5 people) and potentially even blood pressure.
Why This Matters
There are over 7,000 known rare genetic diseases. Most have no treatment. CRISPR is turning “untreatable” into “curable” — and the technology is getting faster, cheaper, and more precise every year.
The first approved CRISPR therapy (Casgevy for sickle cell disease) arrived in 2023. Baby KJ’s personalized cure came in 2025. Epigenetic editing and one-shot cardiovascular treatments are in clinical trials now. We’re watching medicine transform in real time.
Watch the Full Episode
We go much deeper into the science, the delivery problem being solved by nanoparticles, and what Jennifer Doudna herself says about CRISPR’s future. Watch on YouTube or listen on Spotify.
The Story of Baby KJ
KJ was born with CPS1 deficiency — carbamoyl phosphate synthetase 1 deficiency — a condition affecting roughly one in 1.3 million births. His body couldn’t process ammonia, a toxic byproduct of protein metabolism. Without treatment, ammonia would accumulate in his blood and destroy his brain. The standard treatment is a liver transplant, but KJ was too sick to survive the wait list, and even transplant recipients face lifetime immunosuppression and a 10-15% mortality rate.
The team at Children’s Hospital of Philadelphia, led by Dr. Rebecca Ahrens-Nicklas and Dr. Kiran Musunuru, designed a CRISPR-based gene editing therapy from scratch. In just six months, they identified the mutation, designed the guide RNA, tested the approach in cell cultures and animal models, manufactured the lipid nanoparticle delivery vehicle, and received FDA emergency authorization. This timeline — from diagnosis to treatment in six months — was unprecedented.
How the Treatment Works
The therapy uses base editing, a refined version of CRISPR that changes a single letter of DNA without making a double-strand break. Traditional CRISPR-Cas9 cuts both strands of the DNA helix and relies on the cell’s repair machinery to fix the gap — a process that can introduce errors. Base editors, developed by David Liu’s lab at Harvard, chemically convert one DNA base to another (for example, changing an A to a G) with far greater precision.
For KJ, the base editor was packaged inside lipid nanoparticles — the same delivery technology used in mRNA COVID vaccines — and infused intravenously. The nanoparticles were designed to target liver cells, where CPS1 is primarily expressed. Once inside the cell, the base editor corrected the single-letter mutation in the CPS1 gene, restoring the enzyme’s ability to process ammonia.
The Results
Within weeks of treatment, KJ’s ammonia levels dropped from dangerously elevated to near-normal. He went from needing constant hospitalization to going home. At six months post-treatment, he was hitting developmental milestones that his doctors feared he would never reach. The editing appeared stable — the corrected DNA was being passed to new liver cells as they divided.
The key limitation: this is a one-patient drug. The entire development process — mutation identification, guide RNA design, testing, manufacturing — had to be done specifically for KJ’s exact mutation. At current costs and timelines, this approach is only feasible for life-threatening conditions with no other treatment options.
The Broader Revolution: From One Patient to Millions
While KJ’s treatment was bespoke, CRISPR therapies are rapidly scaling to larger patient populations. Casgevy, the first FDA-approved CRISPR therapy (December 2023), treats sickle cell disease and beta-thalassemia — conditions affecting millions worldwide. It works by editing patients’ own blood stem cells to reactivate fetal hemoglobin, bypassing the defective adult hemoglobin gene.
The pipeline is expanding rapidly. CRISPR-based therapies are in clinical trials for hereditary blindness (Editas Medicine’s EDIT-101), high cholesterol (Verve Therapeutics’ heart disease program), HIV (Excision BioTherapeutics), and various cancers (using CRISPR to engineer more effective CAR-T cells). Intellia Therapeutics demonstrated the first in vivo CRISPR editing — directly editing genes inside the body rather than extracting cells, editing them, and reinfusing — for a rare liver disease called transthyretin amyloidosis.
The Ethical Frontier
CRISPR’s precision opens doors that society hasn’t fully grappled with. Somatic editing (changing genes in non-reproductive cells) is broadly accepted because the changes die with the patient. Germline editing (changing embryo DNA) is far more controversial — changes pass to all future generations. In 2018, Chinese scientist He Jiankui was imprisoned for creating the first gene-edited babies, but the underlying technology has only improved since then.
The prospect of “designer babies” — selecting for intelligence, appearance, or athletic ability — remains technically distant but theoretically possible. Current CRISPR technology is best suited for fixing single-gene diseases with clear mutations, not for enhancing complex traits controlled by hundreds of genes. But the trajectory of the technology suggests that what’s impossible today may be routine in a decade.
Why This Matters
CRISPR gene editing represents a fundamental shift in medicine: from treating symptoms to correcting root causes. For the first time in human history, we can rewrite the genetic code that causes disease. The story of baby KJ — a custom drug for a single patient, designed and delivered in six months — demonstrates both the extraordinary potential and the current limitations. As costs drop and techniques improve, CRISPR may eventually become as routine as antibiotics, fundamentally changing what it means to have a “genetic disease.”
Frequently Asked Questions
What is CRISPR and how does it work?
CRISPR-Cas9 is a gene-editing tool that uses a guide RNA to direct the Cas9 enzyme to a specific DNA location, where it makes a precise cut. The cell’s repair mechanisms then either disable the gene or insert new genetic material. It’s faster, cheaper, and more accurate than previous gene-editing methods.
Has CRISPR been used on humans?
Yes, the FDA approved Casgevy (the first CRISPR therapy) in 2023 for sickle cell disease and beta-thalassemia. Since then, CRISPR therapies have been used for hereditary blindness, cancer immunotherapy, and even custom one-patient treatments for ultra-rare genetic conditions.
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