CRISPR-Cas9 was developed by Jennifer Doudna and Emmanuelle Charpentier in 2012, earning them the 2020 Nobel Prize in Chemistry. In the decade since, CRISPR has moved from significant laboratory tool to approved medical therapy — a transition that accelerated sharply in 2023.
## The First Approved CRISPR Therapy
In December 2023, the FDA approved Casgevy (exagamglogene autotemcel, exa-cel), developed by Vertex Pharmaceuticals and CRISPR Therapeutics — the world’s first approved CRISPR gene editing therapy. It targets sickle cell disease (SCD) and transfusion-dependent beta-thalassemia (TDT).
Casgevy uses an ex vivo (outside the body) approach: hematopoietic stem cells are extracted from the patient, edited with CRISPR-Cas9 to knock down a BCL11A enhancer element (reactivating fetal hemoglobin production), and reinfused.
Clinical results were striking: 29 of 29 SCD patients (100%) had no vaso-occlusive crises during a 12-month follow-up; 37 of 39 TDT patients (95%) achieved transfusion independence for at least 12 months. The treatment price is approximately $2.2 million, making it among the most expensive therapies ever approved. See [CRISPR Therapeutics](https://www.crisprtx.com/).
## In Vivo CRISPR: Editing Inside the Body
Ex vivo approaches work well for blood cells and hepatocytes. For diseases of the heart, brain, muscle, or other solid organs, in vivo delivery — getting CRISPR components directly into target cells inside the body — is necessary.
**Intellia Therapeutics** has demonstrated in vivo CRISPR editing of liver cells using lipid nanoparticle delivery, targeting the transthyretin (TTR) gene for treatment of transthyretin amyloidosis (ATTR). Phase I/II data from 2021–2023 showed a single infusion reducing serum TTR levels by up to 93%, with durable effects. See [Intellia clinical data](https://www.intelliatx.com/).
**Ocular applications**: the eye is an ideal in vivo CRISPR target — localized injection, enclosed compartment. Editas Medicine is advancing CRISPR therapy for Leber congenital amaurosis type 10 (LCA10).
## Base Editing and Prime Editing: Higher Precision
Standard CRISPR-Cas9 cuts both DNA strands and relies on cellular repair — a process that can introduce unintended insertions and deletions. Two second-generation technologies improve precision:
**Base editing** (David Liu Lab, MIT/Broad Institute): a modified Cas9 that chemically converts one DNA base to another (C→T or A→G) without cutting the double strand. Dramatically lower off-target mutation rates. Already in early clinical trials for LDL cholesterol reduction (targeting PCSK9).
**Prime editing** (also David Liu Lab): can make virtually any type of precise edit — substitutions, insertions, deletions — without double-strand breaks. Called a “molecular word processor.” Theoretically corrects 89% of known pathogenic variants. Clinical applications are in development.
For deeper background, see [David Liu Lab](https://liugroup.us/), [Broad Institute CRISPR](https://www.broadinstitute.org/crispr), and [Gene Therapy Advances](https://sunqi.org/gene-therapy-advances-en/).
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