Editing genes inside the body has moved from concept to approved therapy, and delivery — not the editor — is now the dominant constraint on what can be treated.

Sources: [1][2]

Evidence standingClinical practice
Key facts
Portal
Genetic Modification
Stage
Clinical, first approvals landed
Evidence
Clinical practice
Reversible
Irreversible
Reviewed
Jun 2026
Read time
8 min
Contents

Page status

Non-liver delivery still limited · Long-term off-target surveillance needed

Key takeaways

  • In vivo editing delivers the editor into the patient rather than editing cells in a lab and reinfusing them.
  • Delivery vehicles — lipid nanoparticles and viral vectors — determine which tissues are reachable.
  • The first approvals prove the concept; broad tissue reach remains the frontier.

Editor versus delivery

The editing tools — CRISPR nucleases, base editors, prime editors — are increasingly precise. The harder problem is getting them into the right cells at the right dose without triggering immunity or hitting the wrong tissue.

Lipid nanoparticles excel at reaching the liver, which is why early in vivo successes cluster around liver-expressed targets. Viral vectors such as AAV reach other tissues but carry payload-size limits and immune considerations.

From proof to practice

An in vivo CRISPR therapy for transthyretin amyloidosis showed durable knockdown of a disease protein after a single infusion, demonstrating that systemic editing could work in people. Ex vivo edited cell therapies for sickle cell disease and beta-thalassemia then reached regulatory approval.

The next expansion depends on delivery: reaching muscle, brain, and other tissues safely, controlling dose, and managing the fact that most editing is permanent. Redosing, off-target surveillance, and long-term follow-up are the practical agenda.

Open questions

  • Which delivery advances unlock tissues beyond the liver?
  • How is long-term safety monitored when edits are permanent?

Watchlist

Signals that would move this entry along the evidence scale.

Non-liver deliveryBase and prime editing in vivoOff-target long-term surveillance

Key terms

References

  1. In vivo CRISPR editing for transthyretin amyloidosis. Gillmore et al., NEJM, 2021
    First clear demonstration of systemic in vivo CRISPR editing in humans.
  2. FDA approves first CRISPR gene therapy (Casgevy). U.S. FDA, 2023
    Approval of exagamglogene autotemcel for sickle cell disease.

Cite this page

Future Human Atlas. “In Vivo Gene Editing and Delivery.” Last reviewed Jun 2026. https://future-human-wiki.vercel.app/articles/in-vivo-gene-editing

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