Genome editing is the introduction of directed modifications in the genome, a process boosted to therapeutic levels by designer nucleases. Building on the experience of ex vivo gene therapy for severe combined immunodeficiencies, it is likely that genome editing of haematopoietic stem/progenitor cells (HSPC) for correction of inherited blood diseases will be an early clinical application. We show molecular evidence of gene correction in a mouse model of primary immunodeficiency. In vitro experiments in DNA-dependent protein kinase catalytic subunit severe combined immunodeficiency (Prkdc scid) fibroblasts using designed zinc finger nucleases (ZFN) and a repair template demonstrated molecular and functional correction of the defect. Following transplantation of ex vivo gene-edited Prkdc scid HSPC, some of the recipient animals carried the expected genomic signature of ZFN-driven gene correction. In some primary and secondary transplant recipients we detected double-positive CD4/CD8 T-cells in thymus and single-positive T-cells in blood, but no other evidence of immune reconstitution. However, the leakiness of this model is a confounding factor for the interpretation of the possible T-cell reconstitution. Our results provide support for the feasibility of rescuing inherited blood disease by ex vivo genome editing followed by transplantation, and highlight some of the challenges.
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http://dx.doi.org/10.1038/s41598-018-26439-9 | DOI Listing |
Biol Sex Differ
January 2025
Department of Laboratory Medicine and Pathology, School of Medicine, University of Washington, Seattle, WA, 98195, USA.
Background: X chromosome inactivation (XCI) is a female-specific process in which one X chromosome is silenced to balance X-linked gene expression between the sexes. XCI is initiated in early development by upregulation of the lncRNA Xist on the future inactive X (Xi). A subset of X-linked genes escape silencing and thus have higher expression in females, suggesting female-specific functions.
View Article and Find Full Text PDFJ Nanobiotechnology
January 2025
Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, China.
Extracellular vesicles (EVs) are membrane-bound vesicles that are shed or secreted from the cell membrane and enveloped by a lipid bilayer. They possess stability, low immunogenicity, and non-cytotoxicity, exhibiting extensive prospects in regenerative medicine (RM). However, natural EVs pose challenges, such as insufficient targeting capabilities, potential biosafety concerns, and limited acquisition pathways.
View Article and Find Full Text PDFCNS Neurosci Ther
January 2025
Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, China.
Background: Adenosine deaminase action on RNA 1 (ADAR1) can convert the adenosine in double-stranded RNA (dsRNA) molecules into inosine in a process known as A-to-I RNA editing. ADAR1 regulates gene expression output by interacting with RNA and other proteins; plays important roles in development, including growth; and is linked to innate immunity, tumors, and central nervous system (CNS) diseases.
Results: In recent years, the role of ADAR1 in tumors has been widely discussed, but its role in CNS diseases has not been reviewed.
Sci Rep
January 2025
Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, Republic of Korea.
Autism spectrum disorder (ASD) affects up to 1 in 59 children, and is one of the most common neurodevelopmental disorders. Recent genomic studies have highlighted the role of rare variants in ASD. This study aimed to identify genes affected by rare variants shared by siblings with ASD and validate the function of a candidate gene FRRS1L.
View Article and Find Full Text PDFTrends Plant Sci
January 2025
Agricultural Biotechnology Division, National Institute for Biotechnology and Genetic Engineering College, Pakistan Institute of Engineering and Applied Sciences (NIBGE-C, PIEAS), Jhang Road, Faisalabad, Pakistan; Jamil ur Rehman Center for Genome Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan. Electronic address:
Prime editing (PE), a precise CRISPR-based method, has worked well in some plants but faces challenges in dicots. Vu and colleagues developed new PE tools that greatly improve PE efficiency in dicots, enabling accurate, heritable genome edits. This advance marks a breakthrough that could revolutionize crop improvement and plant biotechnology.
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