Selected Grantee Publications
Novel Off-Targeting Events Identified After Genome Wide Analysis of CRISPR-Cas Edited Pigs
Redel et al., The CRISPR Journal. 2024.
https://pubmed.ncbi.nlm.nih.gov/38770737/
CRISPR technology has revolutionized the production of unconventional models, such as gene-edited pigs, for both agricultural and biomedical applications; however, concerns remain regarding the possibility of introducing unwanted modifications in the genome. In this study, researchers demonstrate a pipeline to comprehensively identify off-targeting events on a global scale in the genome of three different gene-edited pig models. They confirmed two known off-targeting events and identified other presumably off-target loci. Their work offers a simplified approach to detecting off-targeting events in an unknown genetic background and increases the value of the pig as a preclinical model. Supported by ORIP (R01OD035561) and NIA.
Macrophages Derived From Human Induced Pluripotent Stem Cells (iPSCs) Serve As a High-Fidelity Cellular Model for Investigating HIV-1, Dengue, and Influenza viruses
Yang et al., Journal of Virology. 2024.
https://pubmed.ncbi.nlm.nih.gov/38323811/
Macrophages can be weaponized by viruses to host viral reproduction and support long-term persistence. The most common way of studying these cells is by isolating their precursors from donor blood and differentiating the isolated cells into macrophages. This method is costly and technically challenging, and it produces varying results. In this study, researchers confirmed that macrophages derived from iPSC cell lines—a model that is inexpensive, consistent, and modifiable by genome editing—are a suitable model for experiments involving HIV and other viruses. Macrophages derived from iPSCs are as susceptible to infection as macrophages derived from blood, with similar infection kinetics and phenotypes. This new model offers researchers an unlimited source of cells for studying viral biology. Supported by ORIP (R01OD034046, S10OD021601), NIAID, NIDA, NIGMS, and NHLBI.
Prime Editing–Mediated Correction of the CFTR W1282X Mutation in iPSCs and Derived Airway Epithelial Cells
Li et al., PLOS ONE. 2023.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686454/
Cystic fibrosis (CF) is caused by recessive mutations in the CF transmembrane conductance regulator (CFTR) gene. Correction of nonsense CFTR mutations, which affects 10% of CF patients, via genomic editing represents a promising therapeutic approach. In this study, investigators tested whether prime editing can be applied as a potential therapeutic modality. Induced pluripotent stem cells (iPSCs) from a CF patient homozygous for the CFTR W1282X mutation were used. Studies demonstrated that prime editing corrected mutant allele in iPSCs, which effectively restored CFTR function in iPSC-derived airway epithelial cells and organoids. Supported by ORIP (R01OD01026594).