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Early Phase 1RecruitingNCT06239636

UP421: first-in-human hypoimmune islet transplant without immunosuppression

What this study tests

Early safety study of gene-edited donor islets transplanted without immunosuppression. Published evidence concerns one recipient, with follow-up subsequently reported to 14 months; the registry target is two participants. Detectable insulin secretion at this low dose has not established insulin independence or safety in a larger population.

Editorial review: .

Registry checked: 2026-09-17. Registry’s own update: 2024-12-11.

Most recent recorded citation date: 2024-03-08. Only explicit date metadata is included; an undated citation may be newer. This does not mean every claim was reviewed on that date.

Trial status, labels and access can change between reviews. How we review the evidence · How to read the evidence

Full sources ↓Full discussion ↓Report an issue →

Evidence at a glance

Who can enter the study?
Adults aged 30-45 with T1D for at least five years, diagnosed before age 18, no measurable stimulated C-peptide, and HbA1c at least 70 mmol/mol despite intensive insulin management. Additional antibody, weight, insulin-dose and health criteria apply; see the registry. Registered eligibility ↗Enrollment criteria describe who may enter. They do not establish who was analyzed or the denominator for a reported result.
Reported benefit and results
The 2025 primary report described one recipient with glucose-responsive C-peptide at 12 weeks, without immunosuppression. No immune response was detected against fully HIP-modified cells, while partially edited double-knockout cells elicited an innate immune response. Four adverse events were reported, none serious or attributed to the islet-cell product; lower-arm paresthesia was possibly procedure-related. A 2026 NEJM letter and Sana update report follow-up to 14 months. The recipient remained on insulin; one low-dose case cannot establish clinical effectiveness or uncommon safety risks.Read the result sources and their limitations →
Important harms
Read the reported results, safety discussion and original sources. A separate harms summary is not available; this does not establish safety.
Research access and approval
Study regions: European Union. A trial listing does not establish product approval or current recruitment at a particular site. Check the study’s current entry requirements.
What remains uncertain?
Read the full discussion and original sources for study limitations. Planned endpoints and completion dates are not results.

Research status alone does not establish approval, clinical benefit or local availability. This record cites company or conference reports. Those sources may describe interim findings; their source type is shown in the source list.

Primary endpoints

  • Safety, assessed by number of treatment-related adverse events (CTCAE v5.0)

The full picture

Evidence available

The 2025 report describes one man receiving gene-edited deceased-donor islets in forearm muscle, without immunosuppression. At 12 weeks, the cells produced glucose-responsive C-peptide. Investigators detected no immune response against the fully HIP-modified cells; partially edited double-knockout cells elicited an innate immune response. Four adverse events were reported, none serious or attributed to the islet-cell product; lower-arm paresthesia was possibly procedure-related.2

A 2026 NEJM letter reports longer follow-up. Sana's account of that letter describes persistence of C-peptide to 14 months.34 This is follow-up of the same recipient, not a larger independent cohort.

Limits

The registry plans two participants; that is an enrollment target, not the number with published outcomes. The low-dose recipient remained on insulin. The result supports further investigation of immune evasion but cannot establish insulin independence, full-dose performance or uncommon harms. UP421 uses donor islets; the related SC451 program uses a different, stem-cell-derived product.241

Sources

  1. [1]
    First-in-human Safety Study of Hypoimmune Pancreatic Islet Transplantation in Adult Subjects With Type 1 Diabetes · Trial registry · 2024-03-08 — Registry target: two participants (estimated enrollment), distinct from the one recipient in published reports. Primary endpoint: treatment-related adverse events.

    ClinicalTrials.gov, NCT06239636.

  2. [2]
  3. [3]
    Long-term follow-up of hypoimmune islet transplantation · Peer-reviewed study — Publication metadata verified; detailed follow-up checked against the July 13 sponsor report, not independently retrieved letter full text.

    NEJM follow-up letter (2026).

  4. [4]
    Sana: publication of 14-month UP421 follow-up · Manufacturer

    Sana, July 13, 2026 follow-up announcement.