AI Article Synopsis
- STAT3-hyper IgE syndrome (STAT3-HIES) is a genetic immune disorder causing lung issues and other symptoms.
- CRISPR-Cas9 technology has been utilized to correct a specific mutation (p.R382W) associated with this condition in patient-derived fibroblasts and iPSCs, achieving about 29%-30% correction efficiency without harmful off-target effects.
- The treated cells demonstrated improved STAT3 signaling and maintained their ability to develop into functional alveolar organoids, suggesting ABE-based gene editing could be a promising treatment for STAT3-HIES.
Article Abstract
STAT3-hyper IgE syndrome (STAT3-HIES) is a primary immunodeficiency presenting with destructive lung disease along with other symptoms. CRISPR-Cas9-mediated adenine base editors (ABEs) have the potential to correct one of the most common STAT3-HIES causing heterozygous mutations (c.1144C>T/p.R382W). As a proof-of-concept, we successfully applied ABEs to correct p.R382W in patient fibroblasts and induced pluripotent stem cells (iPSCs). Treated primary STAT3-HIES patient fibroblasts showed a correction efficiency of 29% ± 7% without detectable off-target effects evaluated through whole-genome and high-throughput sequencing. Compared with untreated patient fibroblasts, corrected single-cell clones showed functional rescue of STAT3 signaling with significantly increased STAT3 DNA-binding activity and target gene expression of and . Patient-derived iPSCs were corrected with an efficiency of 30% ± 6% and differentiated to alveolar organoids showing preserved plasticity in treated cells. In conclusion, our results are supportive for ABE-based gene correction as a potential causative treatment of STAT3-HIES.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1089/crispr.2020.0111 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
IL-33, a neutrophil extracellular trap-related gene involved in the progression of diabetic kidney disease.
Inflamm Res
January 2025
Department of Nephrology, First Affiliated Hospital of Naval Medical University, Shanghai Changhai Hospital, Shanghai, China.
Background: Chronic inflammation is well recognized as a key factor related to renal function deterioration in patients with diabetic kidney disease (DKD). Neutrophil extracellular traps (NETs) play an important role in amplifying inflammation. With respect to NET-related genes, the aim of this study was to explore the mechanism of DKD progression and therefore identify potential intervention targets.
View Article and Find Full Text PDFMolecular Stratification of Light-Chain Cardiac Amyloidosis With F-Florbetapir and Ga-FAPI-04 for Enhanced Prognostic Precision.
JACC Cardiovasc Imaging
January 2025
Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Center for Rare Diseases Research, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background: Cardiac involvement in amyloid light chain (AL) amyloidosis significantly influences prognosis, necessitating timely diagnosis and meticulous risk stratification.
Objectives: This prospective study aimed to delineate the molecular phenotypes of AL cardiac amyloidosis (AL-CA) by characterizing fibro-amyloid deposition using F-florbetapir and gallium-68-labeled fibroblast activation protein inhibitor-04 (Ga-FAPI-04) positron emission tomography (PET)/computed tomography (CT) imaging. The authors also proposed a novel molecular stratification methodology for prognosis.
The Complexity and Significance of Fibroblast Growth Factor (FGF) Signaling for FGF-Targeted Cancer Therapies.
Cancers (Basel)
December 2024
Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
Fibroblast growth factors (FGFs) have diverse functions in the regulation of cell proliferation and differentiation in development, tissue maintenance, wound repair, and angiogenesis. The goal of this review paper is to (i) deliberate on the role of FGFs and FGF receptors (FGFRs) in different cancers, (ii) present advances in FGF-targeted cancer therapies, and (iii) explore cell signaling mechanisms that explain how FGF expression becomes dysregulated during cancer development. FGF is often mutated and overexpressed in cancer and the different FGF and FGFR isoforms have unique expression patterns and distinct roles in different cancers.
View Article and Find Full Text PDFGeneration of Bona Fide Human Induced Trophoblast Stem Cells by Direct Reprogramming of Term Umbilical Cord Cells.
Int J Mol Sci
December 2024
Reproductive Biology Laboratory, Amsterdam University Medical Center Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Placentation disorders, including severe preeclampsia and fetal growth restriction, have their origins in early pregnancy, whereas symptoms typically present later on. To investigate the pathogenesis of these diseases, there is a need for a reliable in vitro model system of early placenta development with known pregnancy outcomes. Therefore, we optimized the generation of human induced trophoblast stem cells (iTSCs) from term umbilical cord, enabling non-invasive collection of patient-derived material immediately after birth.
View Article and Find Full Text PDFAtrial Fibrosis in Atrial Fibrillation: Mechanistic Insights, Diagnostic Challenges, and Emerging Therapeutic Targets.
Int J Mol Sci
December 2024
Second Department of Cardiology, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece.
Atrial fibrosis is a hallmark of atrial cardiomyopathy and plays a pivotal role in the pathogenesis of atrial fibrillation (AF), contributing to its onset and progression. The mechanisms underlying atrial fibrosis are multifaceted, involving stretch-induced fibroblast activation, oxidative stress, inflammation, and coagulation pathways. Variations in fibrosis types-reactive and replacement fibrosis-are influenced by patient-specific factors such as age, sex, and comorbidities, complicating therapeutic approaches.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!