From switching off a disease-related gene in the liver to rewriting a tiny genetic error, newer gene-editing technologies are changing what it may mean to treat disease at its source.
Gene editing is no longer confined to cells in a laboratory dish. CRISPR-Cas9 has reached approved clinical use, while newer approaches such as base editing and prime editing have entered early patient-specific treatment or clinical testing in a very small number of cases. The difference between these technologies can be surprisingly easy to picture. CRISPR-Cas9 works like molecular scissors. Base editing changes individual genetic letters. Prime editing acts more like search and replace.
But what does that mean for real patients? Increasingly, the goal is not simply to edit DNA, but to match the right editing strategy to a particular disease, tissue and genetic variant, the central idea behind precision medicine.
1. CRISPR-Cas9: Molecular Scissors Enter the Clinic
CRISPR-Cas9 uses a guide RNA to direct the Cas9 enzyme towards a selected DNA sequence. Cas9 commonly cuts both DNA strands, after which the cell repairs the break. Scientists can exploit this process to disrupt a gene or alter how it functions.
One of the clearest examples comes from sickle cell disease.
Exagamglogene autotemcel, known as exa-cel or Casgevy, does not directly repair the disease-causing HBB mutation. Instead, CRISPR-Cas9 edits a regulatory region of BCL11A in a patient’s own blood-forming stem cells. This reactivates fetal haemoglobin, which helps prevent red blood cells from sickling [1]. In the pivotal study, 29 of 30 valuable participants, or 97%, remained free from severe vaso-occlusive crises for at least 12 consecutive months [1].
Another CRISPR target: the liver
CRISPR can also be delivered directly into the body. Nexiguran ziclumeran, or nex-z, is an investigational CRISPR-Cas9 therapy targeting the TTR gene in liver cells in transthyretin amyloidosis with cardiomyopathy. Instead of repairing the gene, the strategy disrupts it to reduce production of transthyretin.
In a Phase 1 study involving 36 participants, serum TTR levels were reduced by an average of approximately 90% at 12 months after a single intravenous infusion [2].
CRISPR-Cas9: Cut and Modify DNA
| Aspect | CRISPR-Cas9 |
| Simple analogy | Molecular scissors |
| How it works | Guide RNA directs Cas9 to DNA, where it commonly creates a double-strand break. |
| Sickle cell example | Casgevy edits a BCL11A regulatory region to increase fetal haemoglobin. [1] |
| Liver example | Nex-z disrupts TTR in liver cells to reduce transthyretin production. [2] |
| Cancer example | Experimental studies have CRISPR-edited patients’ T cells before returning them to the body. [3] |
| Benefits | Programmable targeting; powerful gene disruption; can be used in vivo or ex vivo; has established clinical applications. |
| Shortcomings | Double-strand breaks can generate unwanted DNA-repair outcomes; off-target editing, delivery and intensive conditioning for some ex vivo treatments remain important challenges. |
| Remember it as | Find → cut → disrupt or repair |
Early cancer studies also demonstrated the feasibility of CRISPR-engineered T cells in patients with refractory cancer, although this should not be interpreted as an established CRISPR cure for cancer [3].
2. Base Editing: Changing One Genetic Letter
What if scientists need to change a genetic letter rather than break both DNA strands?
Base editors combine programmable DNA targeting with an enzyme capable of chemically changing a particular DNA base. A remarkable patient example emerged in 2025.
An infant known publicly as Baby KJ had severe carbamoyl-phosphate synthetase 1, or CPS1, deficiency, a rare urea-cycle disorder that can cause dangerous ammonia accumulation.
Researchers created a personalized adenine base-editing treatment targeting the child’s specific CPS1 variant and delivered it to the liver using lipid nanoparticles. The infant received two infusions at approximately seven and eight months of age. During early follow-up, he tolerated increased dietary protein and reduced nitrogen-scavenging medication despite viral illnesses, with no serious adverse events reported [4]. Importantly, this was one patient, and the investigators stressed that longer follow-up was needed to determine safety and efficacy [4].
Could gene editing reach the lungs?
The lungs illustrate a different challenge: delivery. In 2026, researchers reported biodegradable lipid nanoparticles capable of delivering an RNA-based adenine base editor to lung epithelial cells. Targeting the CFTR G542X mutation restored CFTR expression and chloride-channel function in experimental models, including cystic fibrosis mice [5]. This remains preclinical research, not a gene-editing treatment already demonstrated in people with cystic fibrosis.
3. Prime Editing: Search and Rewrite
Prime editing takes the concept further. A prime editor combines a Cas9 nickase, reverse transcription and prime-editing guide RNA, or pegRNA. The pegRNA directs the editor towards its target while also carrying information specifying the desired genetic change [6]. The original technology demonstrated substitutions, selected insertions and deletions without requiring conventional DNA double-strand breaks or donor DNA templates. [6]
Prime editing reaches patients
A particularly important example involves p47-phox-deficient chronic granulomatous disease (p47-CGD), a rare immune disorder commonly caused by a two-nucleotide deletion in the NCF1 gene.
PM359 uses prime editing to correct this deletion in a patient’s own CD34+ blood-forming stem cells before the edited cells are returned following conditioning.
In the first two reported participants, neutrophils and platelets engrafted promptly, and NADPH oxidase activity was detected in neutrophils within one month. At the reported follow-up, activity had been maintained for six months in one participant and four months in the other [7]. These findings are important, but prime editing remains in early clinical testing, and longer follow-up and more patients are required.
Prime Editing: Search and Rewrite
| Aspect | Prime Editing |
| Simple analogy | Search-and-replace word processor |
| How it works | Cas9 nickase, reverse transcriptase and pegRNA work together to write specified DNA changes. [6] |
| CGD example | PM359 corrects a two-nucleotide NCF1 deletion in patient-derived blood-forming stem cells. [7] |
| Sickle cell example | Prime editing has corrected the pathogenic HBB allele in patient-derived stem cells in preclinical research. [8] |
| Benefits | Avoids conventional double-strand breaks and can make substitutions plus selected small insertions and deletions. |
| Shortcomings | Efficiency varies; delivery is challenging; unwanted editing products can occur; human clinical experience remains very limited. |
| Remember it as | Find → nick → rewrite |
Sickle cell disease provides an especially useful comparison with Casgevy. Experimental prime editing has directly converted the sickle HBB allele towards wild-type HBB in patient-derived blood-forming stem cells, reaching editing frequencies of 15% to 41% before the cells were evaluated after transplantation into mice [8]. This remains pre-clinical rather than an established patient treatment.
4. What These Patient Stories Do and Do Not Show
These cases demonstrate that gene editing is moving beyond laboratory proof of concept. CRISPR-Cas9 has reached established clinical use for severe sickle cell disease, while personalized base editing and prime editing have entered much earlier stages of human treatment and clinical investigation.
They do not mean that genetic diseases can now simply be “rewritten”. Each approach must solve different problems involving delivery, editing efficiency, unintended genetic changes, immune responses and durability. Some treatments also require cells to be removed and edited outside the body, followed by intensive conditioning before they are returned. The clinical evolution is real. But so is the need for careful evidence.
5. Where Does Gene Editing Go Next?
The evolution of gene editing is increasingly about choosing the right tool for the right biological problem.
If disabling a harmful gene is useful, CRISPR-Cas9 may provide an effective strategy. If one DNA letter needs changing, base editing may offer another route. When a defined sequence needs to be rewritten, including certain substitutions or small insertions and deletions, prime editing expands the possibilities.
This is where gene editing begins to intersect with precision medicine: tailoring a treatment strategy to the specific genetic change, affected tissue and biological needs of an individual patient. Rather than applying one approach to every condition, clinicians and researchers may need to match the right editor, guide sequence and delivery system to the right disease—and, in some cases, to a patient’s individual variant. The personalised base-editing treatment developed for Baby KJ’s CPS1 deficiency illustrates this potential, while also showing how early and technically demanding this field remains [4].
The next frontier may therefore depend as much on delivery as on editing itself. Reaching the liver is different from reaching blood-forming stem cells, while organs such as the lungs pose their own barriers.
Frequently Asked Questions: FAQs
1. Is prime editing the same as CRISPR?
Prime editing was developed from CRISPR-based technology but works differently from conventional CRISPR-Cas9. It uses a Cas9 nickase, reverse transcriptase and pegRNA to write specified changes without requiring a conventional double-strand DNA break. [6]
2. Is CRISPR already being used to treat patients?
Yes. CRISPR-Cas9-based exa-cel is used for eligible patients with sickle cell disease, while other CRISPR therapies remain investigational. [1]
3. What is the difference between base editing and prime editing?
Base editing is particularly suited to specific chemical conversions of individual DNA bases. Prime editing can make a broader range of substitutions as well as selected small insertions and deletions. [6]
4. Has prime editing been used in humans?
Yes, prime editing has entered early clinical testing. PM359 has been administered to patients with p47-phox-deficient chronic granulomatous disease, but the published clinical experience remains very small. [7]
5. Can gene editing currently cure every genetic disease?
No. Whether a disease is suitable for gene editing depends on its genetic cause, target cells, available editing technology, delivery method, safety and other clinical considerations.
Bottom Line
CRISPR-Cas9 changed medicine by showing that scientists could programme a molecular system to find and cut DNA. Base editing and prime editing are extending that idea towards increasingly targeted genetic changes.
CRISPR-Cas9: cut | Base editing: change a letter | Prime editing: search and rewrite
Real patients are beginning to show what these technologies may accomplish. But the examples also demonstrate why gene editing cannot be treated as a single universal solution. The future will depend on matching the right editor, target and delivery system to the right disease.
Medical Disclaimer
This article is for general educational purposes only and does not replace medical advice, diagnosis, or treatment. Consult a qualified healthcare professional for personalized advice, particularly if you are pregnant, breastfeeding, managing a health condition, experiencing persistent sleep problems, or taking prescription medication.
About the Author
Fatima Khalid holds a PhD in Biotechnology and is the founder of Winsora. She uses her scientific training to evaluate emerging health and biotechnology research and translate complex scientific findings into accessible, evidence-based content.
Editorial Note
This article summarises peer-reviewed clinical and preclinical gene-editing research available through September 2026. Clinical status varies substantially among the technologies discussed. Approved CRISPR-based treatment should not be confused with investigational base-editing or early prime-editing approaches.
References
[1] Frangoul H, Locatelli F, Sharma A, et al. Exagamglogene Autotemcel for Severe Sickle Cell Disease. New England Journal of Medicine. 2024;390:1649–1662. DOI: 10.1056/NEJMoa2309676.
[2] Fontana M, Solomon SD, Kachadourian J, et al. CRISPR-Cas9 Gene Editing with Nexiguran Ziclumeran for ATTR Cardiomyopathy. New England Journal of Medicine. 2024;391:2231–2241. DOI: 10.1056/NEJMoa2412309.
[3] Stadtmauer EA, Fraietta JA, Davis MM, et al. CRISPR-engineered T cells in patients with refractory cancer. Science. 2020;367:eaba7365. DOI: 10.1126/science.aba7365.
[4] Musunuru K, Grandinette SA, Wang X, et al. Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease. New England Journal of Medicine. 2025;392:2235–2243. DOI: 10.1056/NEJMoa2504747.
[5] Amino acid-derived ionizable lipids enable inhaled base editing for therapeutic gene correction in the lung. Nature Materials. 2026.
[6] Anzalone AV, Randolph PB, Davis JR, et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature. 2019;576:149–157. DOI: 10.1038/s41586-019-1711-4.
[7] Gori JL, Haddad E, Frangoul H, et al. Prime Editing for p47phox-Deficient Chronic Granulomatous Disease. New England Journal of Medicine. 2026;394:1195–1203. DOI: 10.1056/NEJMoa2509807.
[8] Everette KA, Newby GA, Levine RM, et al. Ex vivo prime editing of patient haematopoietic stem cells rescues sickle-cell disease phenotypes after engraftment in mice. Nature Biomedical Engineering. 2023;7:616–628. DOI: 10.1038/s41551-023-01026-0.
