Crispr/Cas9-Mediated Targeting of the Integrin Beta-2 Gene As a Gene-Editing Strategy for Leukocyte Adhesion Deficiency Type I Publisher

Summary: Can gene editing target an inherited immune disorder? Cell experiments confirmed CRISPR edits in ITGB2; patient-relevant testing is still needed. #GeneEditing #Immunodeficiency

Raji S ; Soltaninejad H ; Hosseinkhani S ; Hamidieh A A
Source: Iranian Journal of Medical Sciences Published:2026

Abstract

Background: Leukocyte adhesion deficiency (LAD) is a genetic immunodeficiency that severely impairs the leukocyte adhesion cascade and migration to the sites of infection and inflammation. As a result, the main consequence is recurrent and severe infections with bacteria and fungi, which can lead to death. The most common variant, LAD-I, is due to mutations in the integrin beta 2 (ITGB2) gene responsible for the β2 integrin (CD18) subunit. Corrective strategies based on gene therapy and genome editing are the most promising methods for treating genetic defects. Methods: In the present experimental in vitro study conducted at Tarbiat Modares University, Tehran, Iran, in 2024, we designed a single-guide RNA (sgRNA) for the CRISPR/Cas9 system to target exon 6 of ITGB2 and performed validation experiments. We also investigated peptide nanocarriers as a potential strategy for delivering the CRISPR components. The PX458 plasmid encoding Cas9 and the designed sgRNA was delivered into HEK293T cells, followed by genome-editing analysis. Results: Genome-editing analysis confirmed a measurable level of indel formation at the target locus. Furthermore, the results of MPG nanopeptide production and purification demonstrate the potential of peptide nanocarriers for genome-editing systems. Conclusion: Overall, this work establishes a foundation for subsequent knock-in and gene-correction studies in clinically relevant immune cell models, paving the way for potential LAD-I gene therapy applications. © Iranian Journal of Medical Sciences.