Combining Gene Editing and iPS to Study and Treat Monogenic Autoinflammatory Diseases

NCT07889947 — Recruiting, 6 participants, Istituto Giannina Gaslini

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Registry	NCT07889947, acronym MAGIC
Status	Recruiting
Study type	Observational
Enrollment	6 (Estimated)
Sponsor	Istituto Giannina Gaslini (Other); collaborators: Piano Nazionale di Ripresa e Resilienza (PNRR)
Conditions	Autoinflammatory Disease, Type 1 Interferonopathies
Dates	start 2026-03-25, primary completion 2026-12-31 (estimated), completion 2026-12-31 (estimated), first posted 2026-10-22, last updated 2026-10-22
Locations	2 sites in Italy

-Summary

Type I interferonopathies (T1I) are rare autoinflammatory diseases characterized by dysregulated type I interferon signaling, leading to severe multisystem inflammation, including skin and lung involvement. STING-associated vasculopathy with onset in infancy (SAVI) is an autosomal dominant T1I associated with severe systemic inflammation, skin ulcers, and progressive interstitial lung disease. Current treatments are often insufficient, highlighting the need for novel therapeutic strategies. This project aims to develop patient-derived induced pluripotent stem cell (iPSC) models, combined with somatic cell differentiation and 3D organoid technologies, to investigate SAVI pathogenesis and assess the feasibility and efficacy of gene editing (GE). By enabling precise correction of disease-causing mutations, GE may overcome the limitations of conventional gene replacement approaches and provide a proof of concept for future targeted therapies.

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+Arms and interventions

Arm	Type	Interventions	Description
A patient with a genetically confirmed diagnosis of STING-associated vasculopathy
case controls

+Outcome measures

Primary outcomes

To generate a model of type I interferonopathy to gain insight in STING1 role in nonhematopoietic cells and to explore gene editing as a therapeutic option [through study completion, an average of 2 years]

Secondary outcomes

To generate an isogenic iPSC line-based in vitro model for the V155M SAVI mutation using CRISPR/Cas9 GE and somatic cell differentiation to study organ-specific pathogenic [through study completion, an average of 2 years]
To develop a GE therapy approach using CRISPR/Cas9 base editing and CRISPR/Cas9 to obtain in locus gene correction of STING1 mutation in HSCs (Aim 2) [through study completion, an average of 2 years]

+Eligibility

Sex: All, accepts healthy volunteers

Inclusion Criteria for Patients with SAVI or COPA

* Participants must be at least 1 year of age.
* Participants must have genetically confirmed SAVI or COPA with corresponding clinical manifestations.
* Written informed consent/assent must be signed by the parent(s)/legal guardian(s) and/or the patient, as applicable.

Exclusion Criteria for Patients with SAVI or COPA - Written informed consent/assent has not been signed by the parent(s)/legal guardian(s) and/or the patient, as applicable.

Inclusion Criteria for AID Control Subjects

* Participants must be adults (18 years of age or older), or neonates when umbilical cord blood is collected.
* Participants must have clinical manifestations of an autoinflammatory disease other than SAVI or COPA, as described in https://doi.org/10.3899/jrheum.2023-1209.
* Written informed consent/assent must be signed by the parent(s)/legal guardian(s) and/or the patient, as applicable.

Inclusion Criteria for Healthy Control Subjects

* Participants must be adults (18 years of age or older), or neonates when umbilical cord blood is collected.
* Participants must be healthy, with no acute or chronic medical conditions.
* Participants must have no history of autoimmune, inflammatory, or genetic diseases.
* Written informed consent must be signed by the participant or the parent(s)/legal guardian(s), as applicable.

Exclusion Criteria for Healthy and AID Control Subjects

\- Written informed consent has not been signed by the participant or the parent(s)/legal guardian(s), as applicable.

+Locations (2)

Facility	City	Country	Status
Presidio Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari	Bari	Italy	Recruiting
IRCCS Istituto Giannina Gaslini	Genova	Italy	Recruiting