CRISPR-Cas9-Based Gene Knockout of Immune Checkpoints in Expanded NK Cells.

Natural killer (NK) cell immunotherapy has emerged as a novel treatment modality for various cancer types, including leukemia. The modulation of inhibitory signaling pathways in T cells and NK cells has been the subject of extensive investigation in both preclinical and clinical settings in recent years. Nonetheless, further research is imperative to optimize antileukemic activities, especially regarding NK-cell-based immunotherapies.

Challenges in Gene Therapy for Somatic Reverted Mosaicism in X-Linked Combined Immunodeficiency by CRISPR/Cas9 and Prime Editing.

X-linked severe combined immunodeficiency (X-SCID) is a primary immunodeficiency that is caused by mutations in the interleukin-2 receptor gamma gene. Some patients present atypical X-SCID with mild clinical symptoms due to somatic revertant mosaicism. CRISPR/Cas9 and prime editing are two advanced genome editing tools that paved the way for treating immune deficiency diseases.

Somatic Reversion of a Novel Mutation Resulting in Atypical X-Linked Combined Immunodeficiency.

Mutations of the gene, which encodes for the interleukin-2 receptor common gamma chain (γ, CD132), can lead to X-linked severe combined immunodeficiency (X-SCID) associated with a TBNK phenotype as a result of dysfunctional γ-JAK3-STAT5 signaling. Lately, hypomorphic mutations of the gene have been described causing atypical SCID with a milder phenotype. Here, we report three brothers with low-normal lymphocyte counts and susceptibility to recurrent respiratory infections and cutaneous warts.

Whole-Brain Susceptibility-Weighted Thrombus Imaging in Stroke: Fragmented Thrombi Predict Worse Outcome.

Background And Purpose: The prevalence and clinical importance of primarily fragmented thrombi in patients with acute ischemic stroke remains elusive. Whole-brain SWI was used to detect multiple thrombus fragments, and their clinical significance was analyzed.

Materials And Methods: Pretreatment SWI was analyzed for the presence of a single intracranial thrombus or multiple intracranial thrombi.

Towards automatic MRI volumetry for treatment selection in acute ischemic stroke patients.

In many tertiary clinical care centers, decision-making and treatment selection for acute ischemic stroke is based on magnetic resonance imaging (MRI). The "mismatch" concept aims to segregate the infarct core from potentially salvageable hypo-perfused tissue, the so-called penumbra that is determined from a combination of different MRI modalities. Recent studies have challenged the current concept of tissue at risk stratification targeted to identify the best treatment options for every individual patient.