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Precise correction of Duchenne muscular dystrophy exon deletion mutations by base and prime editing


Abstract
Duchenne muscular dystrophy (DMD) is a fatal muscle disease caused by the lack of dystrophin, which maintains muscle membrane integrity. We used an adenine base editor (ABE) to modify splice donor sites of the dystrophin gene, causing skipping of a common DMD deletion mutation of exon 51 (∆Ex51) in cardiomyocytes derived from human induced pluripotent stem cells, restoring dystrophin expression. Prime editing was also capable of reframing the dystrophin open reading frame in these cardiomyocytes. Intramuscular injection of ∆Ex51 mice with adeno-associated virus serotype-9 encoding ABE components as a split-intein trans-splicing system allowed gene editing and disease correction in vivo. Our findings demonstrate the effectiveness of nucleotide editing for the correction of diverse DMD mutations with minimal modification of the genome, although improved delivery methods will be required before these strategies can be used to sufficiently edit the genome in patients ....

United States , Matrigel Corning , E Welker Addgene , F Zhang Addgene , Millipore Amicon , Versene Gibco , Jackson Immunoresearch , Cosmo Bio , Graphpad Prism Software , Drug Administration , Texas Southwestern Medical Center , Institutional Animal Care , Twist Bioscience , Thermo Fisher Scientific , Tissue Kit , Mini Kit , Bio Rad Laboratories , Boston Children , Hospital Viral Core , Santa Cruz Biotechnology , Gum Tragacanth , Triangle Bioscience , Stemcell Technologies , Innovative Cell Technologies , Nucleofectorx Kit , Vector Laboratories ,

Population genomic evidence of Plasmodium vivax Southeast Asian origin


P. vivax originates from sub-Saharan Africa based on the circulation of its closest genetic relatives (
P. vivax-like) among African great apes. However, the limited number of genetic markers and samples investigated questions the robustness of this hypothesis. Here, we extensively characterized the genomic variations of 447 human
P. vivax strains and 19 ape
P. vivax-like strains collected worldwide. Phylogenetic relationships between human and ape
Plasmodium strains revealed that
P. vivax-like, not included within the radiation of
P. vivax-like. By investigating various aspects of
P. vivax genetic variation, we identified several notable geographical patterns in summary statistics in function of the increasing geographic distance from Southeast Asia, suggesting that ....

Coted Ivoire , Oromia Regional State , Ivory Coast , Centre National De , National Center , College Of Health , Animal Life Administration Of Libreville , Ministry Of Health , Oromia Regional State Health Bureau , National Hospital , Centers For Disease Control , French National Reference Centers , Ethical Clearance Committee Of The Haramaya University , Beckman Coulter , Centre International De Recherches , Saharan Africa , Southeast Asia , Saharan African , Cheikh Zayed Hospital , Action Sanitaire De Nouakchott , Centre National , Ethical Clearance Committee , Haramaya University , Medical Sciences , Animal Life Administration , Disease Control ,