Hemoglobinopathies provide the first clinically validated delivery model for CRISPR therapeutics, and offers a donor-independent alternative to allogeneic hematopoietic stem-cell transplantation without graft rejection or graft-versus-host disease.
Recent developments and refinements in gene transfer and editing technologies for HSPCs are reviewed, while also discussing the critical limitations and hurdles to clinical translation, as recently presented at the New Investigator Committee Gene Therapy webinar.
Kohei Shiroshita, A. Stolz, C. Malouf et al.· Experimental Hematology· 0 citations
This review discusses medicinal chemistry approaches primarily targeting HDAC1/2, LSD1, and DNMT1, with emphasis on inhibitor classes, binding mechanisms, structural features, preclinical evidence, and translational limitations, and how a better understanding of γ-globin repression may guide the development of safer an...
Mateus Mello de Souza, A. R. Pavan, Victor Gabriel de Faria Pastre et al.· European journal of medicina...· 0 citations
Compound heterozygous mutations in GTF3A, encoding transcription factor IIIA, are identified in a patient with CID presenting with profound T-cell lymphopenia, diminished thymic output, and humoral failure, establishing deficiency of GTF3A resulting in combined immunodeficiency (DoGCID) within the spectrum of ribosomop...
An LNP is reported that efficiently delivers reporter mRNA to human HSPCs both in ex vivo and in vivo settings when conjugated with the anti-CD34 antibody (CD34/LNPDP).
Jingjing Du, Zijin Luo, Dan Xie et al.· Nature Biomedical Engineerin...· 2 citations
Overall, ASH 2025 suggests a shift from achieving gene editing to quantifying efficacy, durability, and safety, with standardized biomarker frameworks likely to play an increasingly important role in future clinical translation.