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Short answer: CRISPR-Cas9 is a genome editing technology that cuts DNA at a location chosen by a guide RNA. According to MedlinePlus Genetics, it is faster, cheaper, more accurate and more efficient than other genome editing methods. Its main limits are delivery into cells and tissues, off-target effects, a targeting requirement called the PAM, and, for any use in people, unresolved questions about safety and effectiveness. These pros and cons of genome editing differ for bench research and for clinical use.
What CRISPR-Cas9 is
MedlinePlus Genetics defines genome editing (also called gene editing) as a group of technologies that let scientists change an organism’s DNA. In CRISPR-Cas9, a guide RNA matches the target DNA and binds the Cas9 enzyme, and Cas9 then cuts the DNA at the targeted location. The cell’s own repair machinery adds, deletes or replaces genetic material at the cut site. This page covers the trade-offs; related CASRAI guides cover other Cas systems such as Cas13 and CRISPRa.
Advantages of CRISPR genome editing
- Speed, cost, accuracy and efficiency relative to older tools. MedlinePlus Genetics describes CRISPR-Cas9 as faster, cheaper, more accurate and more efficient than other genome editing methods.
- Programmable targeting. Because a guide RNA matches the target DNA, the site being cut is set by the guide sequence (MedlinePlus Genetics).
- Broad research scope. It is being studied for single-gene disorders such as cystic fibrosis, hemophilia and sickle cell disease, and for complex diseases including cancer, heart disease, mental illness and HIV (MedlinePlus Genetics).
- A first approved therapy. On 2023-12-08 the FDA announced that Casgevy is the first FDA-approved therapy using CRISPR/Cas9, for sickle cell disease in patients 12 years of age and older with recurrent vaso-occlusive crises.
Disadvantages and limits of CRISPR genome editing
A 2024 peer-reviewed review of CRISPR delivery technologies (Rostami et al., Small Science) names the main in vivo challenges as low delivery efficiency, off-target effects and instability. Each limit has a distinct origin:
| Limit | Where it comes from | Source |
|---|---|---|
| Delivery efficiency and instability | Getting the editing components into the right cells in vivo is difficult | Rostami et al. 2024 |
| Off-target effects | Listed among the in vivo challenges of therapeutic genome editing | Rostami et al. 2024 |
| Single-vector packaging | The Cas protein is very large, so it is hard to package into a single vector | Rostami et al. 2024 |
| Targeting constraint | A PAM is required for Cas9’s RNA-guided targeting of genomic loci | Rostami et al. 2024 |
| Viral vector concerns | Immunogenicity, carcinogenesis, limited DNA packaging capacity and scale-up production | Rostami et al. 2024 |
| Safety and effectiveness in people | Scientists are still working to determine whether the approach is safe and effective for use in people | MedlinePlus Genetics |
For how viral vectors carry a transgene and why packaging capacity matters, see viral vector types and how each delivers a transgene.
Research use versus clinical use
The pros and cons of CRISPR are not the same at the bench and in the clinic.
| Question | Research setting | Clinical setting |
|---|---|---|
| What the evidence supports | A faster, cheaper, more accurate and more efficient method than other genome editing approaches (MedlinePlus Genetics) | One FDA-approved CRISPR/Cas9 therapy, Casgevy, for sickle cell disease in patients 12 and older with recurrent vaso-occlusive crises (FDA, 2023-12-08) |
| What remains open | Delivery, off-target effects and instability are listed challenges (Rostami et al. 2024) | Whether the approach is safe and effective for use in people is still being determined for most uses (MedlinePlus Genetics) |
| Reported effects and use today | Genome editing is used in cells and animal models in research labs to understand diseases (MedlinePlus Genetics) | For Casgevy, the FDA lists common side effects of low platelets and white blood cells, mouth sores and nausea, and patients are to be followed in a long-term study |
Somatic versus germline editing
Somatic cells are cells other than egg and sperm. MedlinePlus Genetics notes that changes to germline cells or embryos could be passed to future generations, and that germline and embryo editing is currently illegal in the United States and many other countries. The ethical arguments are covered in CRISPR ethics, and national rules in CRISPR germline editing legal status by country. For the regulatory path of approved products, see FDA approval of gene therapy.
Where it matters for labs and clinics: a planning checklist
Each question below maps to a limit named in the sources listed at the end of this page.
- Which cells or tissues must receive the editing components, and how will they be delivered? (delivery efficiency and instability)
- Does the target site sit next to the PAM that Cas9 requires? (targeting constraint)
- If a viral vector is considered, how do its packaging capacity and immunogenicity fit the Cas protein’s size? (packaging, viral vector concerns)
- Is the work in somatic cells only, and does any plan touch germline cells or embryos, which are illegal to edit in the United States and many other countries? (MedlinePlus Genetics)
Common misunderstandings
- “CRISPR is an approved treatment in general.” The FDA statement concerns one named therapy, Casgevy, for a defined sickle cell disease population. MedlinePlus Genetics states that safety and effectiveness in people are still being determined more broadly.
- “Genome editing and CRISPR are the same thing.” Genome editing is a group of technologies; CRISPR-Cas9 is one of them (MedlinePlus Genetics).
- “Any genome change can be passed on.” Only changes in germline cells or embryos could be passed to future generations; those are the changes that are illegal in the United States and many other countries.
FAQ
What are the pros and cons of CRISPR?
Pros: it is faster, cheaper, more accurate and more efficient than other genome editing methods (MedlinePlus Genetics), and one CRISPR/Cas9 therapy has FDA approval. Cons: delivery efficiency, off-target effects, instability, the PAM requirement and the large size of the Cas protein (Rostami et al. 2024).
What are the pros and cons of genome editing?
The same trade-off applies across genome editing: the technology can change DNA at chosen locations, while safety and effectiveness for use in people are still being determined (MedlinePlus Genetics).
Is genome editing safe?
MedlinePlus Genetics says scientists are still working to determine whether CRISPR-Cas9 is safe and effective for use in people. For the one approved therapy, Casgevy, the FDA lists side effects and requires long-term follow-up of patients.
Sources
- U.S. Food and Drug Administration, FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease, 2023-12-08; checked 2026-10-29.
- MedlinePlus Genetics, What are genome editing and CRISPR-Cas9?; checked 2026-10-29.
- Rostami et al., Exploring Advanced CRISPR Delivery Technologies for Therapeutic Genome Editing, Small Science 2024;4(10):2400192, doi:10.1002/smsc.202400192; checked 2026-10-29.
