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categories: ["genetics"]categories: ["genetics"]tags: ["crispr", "genome editing", "gene therapy", "point mutations", "biotechnology"]tags: ["crispr", "genome editing", "gene therapy", "point mutations", "biotechnology"]summary: "A genome editing method that chemically converts one DNA base into another at a targeted site without cutting both strands of the double helix."summary: "A genome editing method that chemically converts one DNA base into another at a targeted site without cutting both strands of the double helix."updated: "2026-07-27"updated: "2026-10-29"humanEvidence: "All human use is early-phase or one-off: base-edited donor T cells were given to a teenager with relapsed leukaemia in 2022, in vivo liver editing has lowered cholesterol in early trials, and a bespoke editor was dosed into one infant."humanEvidence: "All human use is early-phase or one-off: base-edited donor T cells were given to a teenager with relapsed leukaemia in 2022, in vivo liver editing has lowered cholesterol in early trials, and a bespoke editor was dosed into one infant."access: "No base-editing therapy is approved anywhere as of 2026; the only routes are early-phase clinical trials and one-off bespoke treatments authorised for a single patient."access: "No base-editing therapy is approved anywhere as of 2026; the only routes are early-phase clinical trials and one-off bespoke treatments authorised for a single patient."reversibility: "irreversible"reversibility: "irreversible"lines 19–25 → 19–254 unchanged lines not shown
{{ "caption": "Genome editing platform", "caption": "Genome editing platform", "rows": [ "rows": [ { "label": "Type", "value": "Deaminase–nickase fusion" }, { "label": "Type", "value": "Deaminase-nickase fusion" }, { "label": "First described", "value": "2016 (cytosine), 2017 (adenine)" }, { "label": "First described", "value": "2016 (cytosine), 2017 (adenine)" }, { "label": "Developed by", "value": "David Liu laboratory" }, { "label": "Developed by", "value": "David Liu laboratory" }, { "label": "Edits possible", "value": "4 of 12 substitutions" }, { "label": "Edits possible", "value": "4 of 12 substitutions" },lines 66–81 → 66–8140 unchanged lines not shown
As of 2026, base editing is in clinical trials rather than approved practice, and the trials divide into two families.As of 2026, base editing is in clinical trials rather than approved practice, and the trials divide into two families. Ex vivo programmes edit cells outside the body and return them. A sickle cell disease candidate uses an adenine editor to recreate a naturally occurring promoter variant that keeps fetal haemoglobin switched on in adulthood — a different route to the same physiological end as [[casgevy]], which disrupts an erythroid enhancer of the repressor gene *BCL11A* instead. Both approaches share the burden that limits autologous stem cell therapy generally: patients need conditioning chemotherapy to clear marrow space, and that conditioning carries real mortality and infertility risk independent of the edit.Ex vivo programmes edit cells outside the body and return them. A sickle cell disease candidate uses an adenine editor to recreate a naturally occurring promoter variant that keeps fetal haemoglobin switched on in adulthood. That is a different route to the same physiological end as [[casgevy]], which disrupts an erythroid enhancer of the repressor gene *BCL11A* instead. Both approaches share the burden that limits autologous stem cell therapy generally: patients need conditioning chemotherapy to clear marrow space, and that conditioning carries real mortality and infertility risk independent of the edit. In vivo programmes deliver the editor systemically, almost always to the liver, using [[lipid-nanoparticles]]. The first in-human in vivo base editing trial, run by Verve Therapeutics, disabled *PCSK9* in hepatocytes to lower LDL cholesterol permanently; a successor candidate from the same programme reported substantial cholesterol reductions in 2025. A separate liver programme has reported correction — as opposed to disruption — of a disease-causing point mutation in patients with alpha-1 antitrypsin deficiency, which if it holds up would be the first such correction in a person.In vivo programmes deliver the editor systemically, almost always to the liver, using [[lipid-nanoparticles]]. The first in-human in vivo base editing trial, run by Verve Therapeutics, disabled *PCSK9* in hepatocytes to lower LDL cholesterol permanently; a successor candidate from the same programme reported substantial cholesterol reductions in 2025. A separate liver programme has reported correction (as opposed to disruption) of a disease-causing point mutation in patients with alpha-1 antitrypsin deficiency, which if it holds up would be the first such correction in a person. > [!key] The bespoke-therapy case> [!key] The bespoke-therapy case> In 2025 clinicians at the Children's Hospital of Philadelphia treated an infant with a severe urea-cycle disorder using a base editor designed for his specific mutation and delivered by lipid nanoparticle, from diagnosis to dosing in roughly six months.[^musunuru2025] It is the clearest existing demonstration that editing can be personalised, and the clearest illustration that regulatory and manufacturing pathways for one-patient medicines do not yet exist.> In 2025 clinicians at the Children's Hospital of Philadelphia treated an infant with a severe urea-cycle disorder using a base editor designed for his specific mutation and delivered by lipid nanoparticle, from diagnosis to dosing in roughly six months.[^musunuru2025] The case is the clearest existing demonstration that an editor can be designed for one person, and the clearest illustration that regulatory and manufacturing pathways for one-patient medicines do not yet exist. ## Limitations## Limitations The four accessible substitutions are the transitions — C to T, G to A, A to G, T to C. The eight transversions require different chemistry. Glycosylase-based editors that produce C-to-G changes exist but are less efficient and less clean, and for most transversions [[prime-editing]] remains the practical option.The four accessible substitutions are the transitions: C to T, G to A, A to G, T to C. The eight transversions require different chemistry. Glycosylase-based editors that produce C-to-G changes exist but are less efficient and less clean, and for most transversions [[prime-editing]] remains the practical option. Targeting is still constrained by the PAM requirement inherited from Cas9, which limits how the editing window can be positioned over a given base. Cargo size is a problem for viral delivery: a base editor plus guide RNA exceeds the packaging capacity of a single [[aav-vectors|adeno-associated virus]], forcing split-vector designs. And systemic delivery beyond liver and haematopoietic cells remains largely unsolved, which is the same constraint that limits [[targeted-drug-delivery]] generally.Targeting is still constrained by the PAM requirement inherited from Cas9, which limits how the editing window can be positioned over a given base. Cargo size is a problem for viral delivery: a base editor plus guide RNA exceeds the packaging capacity of a single [[aav-vectors|adeno-associated virus]], forcing split-vector designs. And systemic delivery beyond liver and haematopoietic cells remains largely unsolved, which is the same constraint that limits [[targeted-drug-delivery]] generally. lines 89–95 → 89–957 unchanged lines not shown
## Outlook## Outlook The near-term question is whether permanent single-dose edits to common risk genes — a lifetime cholesterol reduction from one infusion, for instance — can clear a safety bar set for chronic disease rather than for fatal rare disease. That bar is high, because the comparator is a cheap daily pill and the edit is irreversible. The technical frontier is delivery to tissues other than liver, editors small enough for single-vector packaging, and reliable assays for scattered off-target deamination. The economic frontier, shared with [[gene-therapy-for-aging]] and every other one-time genetic medicine, is whether a treatment designed for one child can ever be paid for, a problem that runs directly into [[access-and-inequality]] and that no current reimbursement system is built to solve.The near-term question is whether permanent single-dose edits to common risk genes, such as a lifetime cholesterol reduction from one infusion, can clear a safety bar set for chronic disease rather than for fatal rare disease. That bar is high, because the comparator is a cheap daily pill and the edit is irreversible. The technical frontier is delivery to tissues other than liver, editors small enough for single-vector packaging, and reliable assays for scattered off-target deamination. The economic frontier, shared with [[gene-therapy-for-aging]] and every other one-time genetic medicine, is whether a treatment designed for one child can ever be paid for, a problem that runs directly into [[access-and-inequality]] and that no current reimbursement system is built to solve. ## See also## See also removed, struck through added, underlinedLine numbers count the serialised markdown of each revision, frontmatter included.
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