Publications by authors named "J Scholefield"
We are often confronted with a simple question, "which gene editing technique is the best?"; the simple answer is "there isn't one". In 2021, a year after prime editing first made its mark, we evaluated the landscape of this potentially transformative advance in genome engineering towards getting treatments to the clinic [1]. Nearly 20% of the papers we cited were still in pre-print at the time which serves to indicate how early-stage the knowledge base was at that time.
View Article and Find Full Text PDFCRISPR-Cas9 mediated knockout of NDUFS4 in human iPSCs: A model for mitochondrial complex I deficiency.
Biochim Biophys Acta Mol Basis Dis
February 2025
Article Synopsis
- Mitochondrial diseases, particularly those linked to complex I defects, currently have no cure, highlighting the need for better drug discovery methods.
- *Induced pluripotent stem cells (iPSCs) can be genetically modified using CRISPR-Cas9, creating models like the NDUFS4 knockout (KO) that exhibit significant metabolic changes linked to mitochondrial dysfunction.
- *Metabolomic profiling of NDUFS4 KO iPSCs revealed an increased NADH/NAD ratio, and treatment with β-lapachone improved the redox state, emphasizing the potential of iPSCs for developing new therapies for mitochondrial disorders.*
Article Synopsis
- The CRISPR-Cas9 system has revolutionized genome engineering due to its ease of use, leading to a Nobel Prize win in Chemistry in 2020 for its developers.
- *Recent advancements in gene therapy, particularly in the Global North, showcase its potential benefits in treating diseases like sickle cell anaemia and improving transplant options.
- *However, challenges in the Global South, such as funding limitations and a shortage of skilled professionals, hinder the adoption of this technology, emphasizing the need for cost-effective methods and increased accessibility.*
Human induced pluripotent stem cell-derived models are a well-established preclinical tool, with the ability to retain the genetics of the individual from which they are derived. Here we comment on the global representation and accessibility of such cellular tools from African population groups.
View Article and Find Full Text PDFThe lack of equitable representation of African diversity in scientific resources, such as genome-wide association studies and human induced pluripotent stem cell (hiPSC) repositories, has perpetuated inequalities in the advancement of health research. HiPSCs could be transformative in regenerative and precision medicine, therefore, the generation of diverse lines is critical in the establishment of African-relevant preclinical cellular models. HiPSC lines were derived from two healthy donors of Black African ancestry using Sendai virus reprogramming of dermal fibroblasts, and characterised to confirm stemness markers, trilineage differentiation, and genetic integrity.
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