Genome editing for primary immunodeficiencies: A therapeutic perspective on Wiskott-Aldrich syndrome

Naseem, Asma; Steinberg, Zohar; Cavazza, Alessia

doi:10.3389/fimmu.2022.966084

Cited by 8 publications

(6 citation statements)

References 131 publications

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“…X-linked Wiskott–Aldrich syndrome (WAS), first recognized in 1937 by Dr. Alfred Wiskott, and then in 1957, confirmed by Robert Aldrich [ 39 ].it is estimated to involve 1–10 live births per million males. The WAS gene encodes a cytosolic protein known as WAS protein (WASp) and it expressed in myeloid, lymphoid, and hematopoietic stem cells (HSCs), which can lead to various clinical manifestations, but thrombocytopenia (X-linked thrombocytopenia [XLT]), eczema, and recurrent infections with increased risk of lymphoid malignancies, autoimmune disorders or congenital neutropenia (X-lined neutropenia [XLN]) are classic phenotype of WAS [ 40 , 41 ].…”

Section: Combined Immunodeficiency (Cid)mentioning

confidence: 99%

Inborn errors of immunity with kidney and urinary tract disorders: a review

Shajari,

Zare Ahmadabadi,

Ashrafi

et al. 2024

Int Urol Nephrol

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Human inborn errors of immunity (IEIs), previously referred to as primary immunodeficiency disorders (PIDs), are a heterogeneous spectrum of inherited abnormalities of the immune system with different organ involvement. The number of identified IEIs is rapidly increasing, highlighting the non-negligible role of an interdisciplinary approach in clinical diagnosis. Kidney disorders are one of the important comorbidities in some of the affected patients and play a significant role in the diagnosis and course of disease. According to recent studies, 22 types of human IEI with renal manifestations have been identified so far, including immunodeficiency with congenital thrombocytopenia, thymic defects with additional congenital anomalies, complement deficiencies, type 1 interferonopathies, immunity related to non-hematopoietic tissues, congenital neutropenia’s, common variable immunodeficiency disorder (CVID) phenotype and immuno-osseous dysplasia. Based on this classification, we herein review IEIs with renal features and explain the genetic defect, inheritance, and type of renal manifestations.

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Section: Combined Immunodeficiency (Cid)mentioning

confidence: 99%

Inborn errors of immunity with kidney and urinary tract disorders: a review

Shajari,

Zare Ahmadabadi,

Ashrafi

et al. 2024

Int Urol Nephrol

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“…Gene therapy for WAS has been rapidly developed in recent years and its therapeutic effect has been widely recognize (15,16). Gene therapy involves gene editing of autologous hematopoietic stem cells and reinfusion, which avoids the risks of allogeneic transplantation and effectively overcomes the realistic obstacles of bone marrow matching (17,18).…”

Section: Correspondencementioning

confidence: 99%

Wiskott-Aldrich syndrome: A new synonym mutation in the WAS gene

Sun,

Song,

Pan

et al. 2024

IRDR

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Wiskott-Aldrich syndrome, synonymous mutation, newborn, hematopoietic stem cell transplantation, intracranial hemorrhage Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive primary immunodeficiency disorder. Mutations in the WAS gene are considered to be the primary cause of WAS. In this work, we report a boy who presented with intracranial hemorrhage (ICH) as an initial symptom and detects a novel pathogenic synonymous mutation in his WAS gene. His mother was a carrier of the mutant gene. The mutation, located at position c.273 (c.273 G>A) in exon 2, is a synonym mutation and predicted to affect protein expression by disrupting gene splicing. This study summarizes the diagnosis and treatment process of the patient and expands the genetic spectrum of WAS.

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“…Despite the ability of genome-editing nucleases to induce site-specific targeted editing, undesired on- and off-target editing (and the effects associated with it) remain a significant issue [ 107 , 108 ]. In the case of CRISPR-Cas9, off-target editing occurs as a result of mismatched bases between the gRNA and DNA sequence being tolerated and still inducing a Cas9 DSB.…”

Section: Existing Barriers To Efficient Hdr-based Therapiesmentioning

confidence: 99%

Homology-Directed-Repair-Based Genome Editing in HSPCs for the Treatment of Inborn Errors of Immunity and Blood Disorders

et al. 2023

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Genome engineering via targeted nucleases, specifically CRISPR-Cas9, has revolutionized the field of gene therapy research, providing a potential treatment for diseases of the blood and immune system. While numerous genome editing techniques have been used, CRISPR-Cas9 homology-directed repair (HDR)-mediated editing represents a promising method for the site-specific insertion of large transgenes for gene knock-in or gene correction. Alternative methods, such as lentiviral/gammaretroviral gene addition, gene knock-out via non-homologous end joining (NHEJ)-mediated editing, and base or prime editing, have shown great promise for clinical applications, yet all possess significant drawbacks when applied in the treatment of patients suffering from inborn errors of immunity or blood system disorders. This review aims to highlight the transformational benefits of HDR-mediated gene therapy and possible solutions for the existing problems holding the methodology back. Together, we aim to help bring HDR-based gene therapy in CD34+ hematopoietic stem progenitor cells (HSPCs) from the lab bench to the bedside.

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Genome editing for primary immunodeficiencies: A therapeutic perspective on Wiskott-Aldrich syndrome

Cited by 8 publications

References 131 publications

Inborn errors of immunity with kidney and urinary tract disorders: a review

Inborn errors of immunity with kidney and urinary tract disorders: a review

Wiskott-Aldrich syndrome: A new synonym mutation in the WAS gene

Homology-Directed-Repair-Based Genome Editing in HSPCs for the Treatment of Inborn Errors of Immunity and Blood Disorders

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