WVE-006 by Wave Life Sciences: status and timeline

WVE-006

First-in-human ADAR-mediated RNA editing therapy for alpha-1 antitrypsin deficiency using AAV vector. Edits endogenous AATD mRNA to produce functional protein.

ProtoStage 2 of 5

Phase 1 done; RestorAATion-2 registrational trial with interim analysis for accelerated approval.

Updated Mar 2026Checked 10 Oct0 updates this week

Milestones

Next · RestorAATion-2 registrational trial initiated

Phase 1 trial completedFeb 2025Complete.
RestorAATion-2 registrational trial initiatedTarget 2025Current milestone.
Interim analysis for accelerated approvalTarget 2027Not yet reached.

Most important updates

Wave reports Phase 1 durability for WVE-006; advances RestorAATion-2 registrational trialMar 2026

Upcoming

2025RestorAATion-2 registrational trial initiated (next)
2027Interim analysis for accelerated approval

Current obstacles

Durability of editing after single doseUnclear whether one AAV administration creates permanent edits or requires repeat dosing as ADAR expression decays.
Off-target editingADAR can edit unintended sites; balancing on-target efficiency with off-target minimization is being optimized.

Physics limits

AAV payload limits restrict guide array sizeAAV serotypes targeting liver have ~4.7 kb capacity; large guide designs need multiple vectors or alternative delivery.
Immune response to foreign ADAR enzymePatients may mount T-cell responses against ADAR; pre-existing AAV immunity also limits eligible population.

How it works

3 parts

Vector delivery

AAV carries ADAR and guide RNA

Engineered AAV delivers both ADAR enzyme and guide sequences that direct editing to specific mRNA targets.

In-situ editing

Edit mRNA without changing DNA

ADAR converts adenosine to inosine in mRNA, read as guanosine; stop codons become sense, enabling translation.

Therapeutic effect

Cells produce functional AATD protein

Edited transcript produces alpha-1 antitrypsin; single treatment could replace decades of weekly infusions if durable.

Spec sheet

Spec	WVE-006
Mechanism	ADAR-mediated RNA editing^R (reported)
Delivery	Adeno-associated virus (AAV)^R (reported)
Target	SERPINA1 mRNA (alpha-1 antitrypsin)^R (reported)

^R reported by the company

Update log

1 update

Mar 2026

Major: Wave reports Phase 1 durability for WVE-006; advances RestorAATion-2 registrational trialPressTest

About Wave Life Sciences

The team behind WVE-006

Wave Life Sciences

RNA medicines, PRISM, ADAR editing, siRNA therapies

Wave develops RNA medicines using its PRISM platform for gene editing, RNA interference, and antisense silencing. Lead programs: WVE-006 (ADAR editing for alpha-1 antitrypsin deficiency) and WVE-007 (siRNA for obesity).

PRISM platform combines RNA editing, splicing, RNAi, and antisense silencing.
WVE-006 is first clinical ADAR therapy; interim data supports accelerated FDA approval path.
WVE-007 twice-yearly siRNA for obesity shows durable weight loss while sparing muscle.

wavelifesciences.com (opens wavelifesciences.com)Company profile →

Headquarters: United States
Status: Public
Valuation: public
Works in: BiotechGene editing & therapy
Coverage: 2 programs · 2 updateslatest 1 Mar 2026checked 10 Oct

Spec

WVE-006

Mechanism

ADAR-mediated RNA editing^R (reported)

Delivery

Adeno-associated virus (AAV)^R (reported)

Target

SERPINA1 mRNA (alpha-1 antitrypsin)^R (reported)