Gene therapy and gene editing are two of the most transformative — and most frequently confused — technologies in modern biotechnology. Both operate at the level of DNA and both aim to treat disease by addressing its genetic roots. But they work in fundamentally different ways, and that difference has important implications for which diseases they can treat, what the manufacturing challenges are, and how to evaluate the clinical and commercial prospects of companies developing them. For biotech investors, understanding the distinction between gene therapy and gene editing is essential for accurately reading pipeline descriptions and company profiles.
The Short Answer
| Gene therapy delivers a functional copy of a gene — or a gene that performs a therapeutic function — into a patient’s cells, typically using a viral vector as the delivery vehicle. It does not change the patient’s existing DNA; it adds new genetic material that compensates for a defective or missing gene. Gene editing, by contrast, makes deliberate changes to the patient’s existing DNA sequence — correcting, disabling, or modifying specific genetic sequences using molecular tools such as CRISPR-Cas9. Both approaches can achieve similar clinical goals, but through mechanistically different means. |
Two Scientific Traditions That Converged in the Clinic
The concept of gene therapy — delivering working genes to correct disease — dates to the 1970s, shortly after the discovery of recombinant DNA technology. The first human gene therapy trial was conducted in 1990 by Michael Blaese and W. French Anderson at the NIH, treating two children with adenosine deaminase deficiency — a rare immune disorder. The trial produced limited but encouraging results, initiating an era of intense clinical activity.
Gene therapy’s first major crisis came in 1999 when Jesse Gelsinger, an 18-year-old patient in a gene therapy trial at the University of Pennsylvania, died from a severe immune reaction to the adeno-associated virus (AAV) vector used to deliver the therapeutic gene. The death halted the field for years and triggered fundamental rethinking of vector design and patient selection.
Gene editing developed along a parallel track, primarily in academic research settings, with CRISPR-Cas9 emerging in 2012 as the first truly practical, programmable editing tool. The two traditions converged in the clinic by the mid-2010s as both gene therapy vectors and gene editing tools were being deployed in clinical trials, sometimes in combination — for example, using viral vectors to deliver CRISPR components for in vivo editing.
How Gene Therapy Delivery Works — Viral Vectors
Most gene therapies use a viral vector — a virus that has been modified to remove its disease-causing components while retaining its natural ability to enter cells and deliver genetic material. The two most widely used vector types are adeno-associated virus (AAV) and lentiviral vectors. AAV vectors are used for many in vivo gene therapies — therapies delivered directly into the patient’s body — targeting tissues including the liver, eye, muscle, and central nervous system. AAV has a favorable safety profile and does not integrate into the host genome in most target tissues, reducing the risk of insertional mutagenesis.
Lentiviral vectors are retroviruses that integrate their genetic cargo into the host cell’s genome, providing durable expression. They are used primarily for ex vivo gene therapies — where cells are removed from the patient, transduced in the laboratory, and reinfused. CAR-T cell therapy often uses lentiviral vectors to deliver the chimeric antigen receptor gene. The integration of lentiviral vectors is generally into transcriptionally active regions of the genome, which historically raised insertional oncogenesis concerns addressed through improved vector design.
The Key Clinical Differences
Gene therapy is additive — it adds new genetic material without removing or altering what is already there. This means it can compensate for a non-functional gene but cannot remove or correct a dominant-negative mutation — a mutation where the defective gene actively causes harm rather than simply being absent. For dominant diseases, gene editing — which can directly disable or correct the mutant sequence — is the more appropriate approach.
Gene editing is precise but requires effective delivery to the target tissue, which is currently the primary limiting factor for in vivo editing applications. AAV-delivered CRISPR, for example, can edit liver cells effectively after intravenous infusion but faces major challenges in reaching solid tumor cells, neurons, and many other tissues. This delivery constraint means that the near-term clinical success of in vivo gene editing is largely concentrated in liver-targeting applications.
First Approvals and Where the Field Stands
The FDA approved its first gene therapy — Spark Therapeutics’ Luxturna, for a rare inherited form of blindness caused by RPE65 mutations — in December 2017. Novartis’ Zolgensma, an AAV-based gene therapy for spinal muscular atrophy, followed in 2019 and became the world’s most expensive drug at launch. On the gene editing side, Casgevy — the first CRISPR-based therapy, developed by Vertex and CRISPR Therapeutics — received FDA approval in December 2023.
As of 2025, the pipeline of both gene therapy and gene editing programs in clinical development is broad and growing, with significant activity in hemophilia, rare metabolic diseases, rare neurological conditions, and multiple oncology applications.
What This Does Not Guarantee
| Neither gene therapy nor gene editing guarantees clinical success. Both approaches face technical risks around delivery efficiency, durability of expression, immune reactions to viral vectors or editing components, and off-target effects. Gene therapy durability — how long the therapeutic effect lasts — has been a clinical challenge in some applications, as AAV vectors do not replicate and may dilute in dividing cells. Manufacturing is complex, expensive, and a significant commercial constraint for both approaches. The field has also experienced fatalities; investor enthusiasm must be grounded in rigorous evaluation of the specific technology, target tissue, delivery approach, and clinical data. |
Key Takeaways
- Gene therapy adds functional genetic material to cells using viral vectors (usually AAV or lentiviral); gene editing changes existing DNA sequences using molecular tools like CRISPR
- Gene therapy is additive; gene editing is corrective — the distinction matters for which diseases each can treat
- AAV vectors are used for in vivo gene therapy (delivered directly into the body); lentiviral vectors are used primarily for ex vivo approaches (cells removed, modified, reinfused)
- The first FDA-approved gene therapy was Luxturna (Spark Therapeutics) in 2017 for an inherited retinal disease; the first gene editing therapy was Casgevy (Vertex/CRISPR Therapeutics) in 2023
- In vivo gene editing delivery is currently most effective for liver-targeting applications; reaching other tissues remains a significant technical challenge
- Manufacturing complexity and cost are major commercial constraints for both gene therapy and gene editing products
- Durability of therapeutic effect, immune reactions to vectors, and off-target editing are active safety and clinical risks across both approaches
Sources
1. FDA — Luxturna Approval: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/luxturna-voretigene-neparvovec-rzyl
2. FDA — Zolgensma Approval: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/zolgensma-onasemnogene-abeparvovec-xioi
3. FDA — Casgevy Approval: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/casgevy
4. NIH — Gene Therapy: https://www.genome.gov/Genetic-Disorders/Gene-Therapy
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