{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Davis JR"],"funding":["U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences","Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)","U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)","Howard Hughes Medical Institute","U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)","U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)","U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute","Bill and Melinda Gates Foundation","Howard Hughes Medical Institute (HHMI)"],"pagination":["1272-1283"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9652153"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6(11)"],"pubmed_abstract":["The viral delivery of base editors has been complicated by their size and by the limited packaging capacity of adeno-associated viruses (AAVs). Typically, dual-AAV approaches based on trans-splicing inteins have been used. Here we show that, compared with dual-AAV systems, AAVs with size-optimized genomes incorporating compact adenine base editors (ABEs) enable efficient editing in mice at similar or lower doses. Single-AAV-encoded ABEs retro-orbitally injected in mice led to editing efficiencies in liver (66%), heart (33%) and muscle (22%) tissues that were up to 2.5-fold those of dual-AAV ABE8e, and to a 93% knockdown (on average) of human PCSK9 and of mouse Pcsk9 and Angptl3 in circulation, concomitant with substantial reductions of plasma cholesterol and triglycerides. Moreover, three size-minimized ABE8e variants, each compatible with single-AAV delivery, collectively offer compatibility with protospacer-adjacent motifs for editing approximately 82% of the adenines in the human genome. ABEs encoded within single AAVs will facilitate research and therapeutic applications of base editing by simplifying AAV production and characterization, and by reducing the dose required for the desired level of editing."],"journal":["Nature biomedical engineering"],"pubmed_title":["Efficient in vivo base editing via single adeno-associated viruses with size-optimized genomes encoding compact adenine base editors."],"pmcid":["PMC9652153"],"funding_grant_id":["R35GM118062","U01AI142756","Liu Grant","UG3AI150551","Liu Investigatorship","RM1HG009490"],"pubmed_authors":["Davis JR","Witte IP","Seidah NG","Musunuru K","Raguram A","Wang X","Liu DR","Banskota S","Huang TP","Levy JM"],"additional_accession":[]},"is_claimable":false,"name":"Efficient in vivo base editing via single adeno-associated viruses with size-optimized genomes encoding compact adenine base editors.","description":"The viral delivery of base editors has been complicated by their size and by the limited packaging capacity of adeno-associated viruses (AAVs). Typically, dual-AAV approaches based on trans-splicing inteins have been used. Here we show that, compared with dual-AAV systems, AAVs with size-optimized genomes incorporating compact adenine base editors (ABEs) enable efficient editing in mice at similar or lower doses. Single-AAV-encoded ABEs retro-orbitally injected in mice led to editing efficiencies in liver (66%), heart (33%) and muscle (22%) tissues that were up to 2.5-fold those of dual-AAV ABE8e, and to a 93% knockdown (on average) of human PCSK9 and of mouse Pcsk9 and Angptl3 in circulation, concomitant with substantial reductions of plasma cholesterol and triglycerides. Moreover, three size-minimized ABE8e variants, each compatible with single-AAV delivery, collectively offer compatibility with protospacer-adjacent motifs for editing approximately 82% of the adenines in the human genome. ABEs encoded within single AAVs will facilitate research and therapeutic applications of base editing by simplifying AAV production and characterization, and by reducing the dose required for the desired level of editing.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Nov","modification":"2025-04-22T19:00:09.278Z","creation":"2025-04-06T02:39:50.653Z"},"accession":"S-EPMC9652153","cross_references":{"pubmed":["35902773"],"doi":["10.1038/s41551-022-00911-4"]}}