{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["16(1)"],"submitter":["De Souza Cordeiro LM"],"funding":["there is no funding"],"pubmed_abstract":["Off-target biodistribution of biologics bears important toxicological consequences. Antibody fragments intended for use as vectors of cytotoxic payloads (e.g. antibody-drug conjugates, radiotherapy) can accumulate at clearance organs like kidneys and liver, where they can cause dose-limiting toxicities. Renal and hepatic uptakes are known to be affected by protein electrostatics, which promote protein internalization through pinocytosis. Using minibodies as a model of an antibody fragment lacking FcRn recycling, we compared the biodistributions of leads with different degrees of accumulation at the kidney and liver. We identified a positive electrostatic patch highly conserved in a germline family very commonly used in the humanization of approved biologics. Neutralization of this patch le"],"journal":["mAbs"],"pagination":["2311991"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10860348"],"repository":["biostudies-literature"],"pubmed_title":["Electrostatic properties of human germlines and biodistribution of small biologics."],"pmcid":["PMC10860348"],"pubmed_authors":["Aivazian A","Atkinson KC","De Souza Cordeiro LM","Joyce PF","Mascioni A","Jia F"],"additional_accession":[]},"is_claimable":false,"name":"Electrostatic properties of human germlines and biodistribution of small biologics.","description":"Off-target biodistribution of biologics bears important toxicological consequences. Antibody fragments intended for use as vectors of cytotoxic payloads (e.g. antibody-drug conjugates, radiotherapy) can accumulate at clearance organs like kidneys and liver, where they can cause dose-limiting toxicities. Renal and hepatic uptakes are known to be affected by protein electrostatics, which promote protein internalization through pinocytosis. Using minibodies as a model of an antibody fragment lacking FcRn recycling, we compared the biodistributions of leads with different degrees of accumulation at the kidney and liver. We identified a positive electrostatic patch highly conserved in a germline family very commonly used in the humanization of approved biologics. Neutralization of this patch le","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jan-Dec","modification":"2026-06-01T17:25:56.786Z","creation":"2024-11-14T12:55:34.392Z"},"accession":"S-EPMC10860348","cross_references":{"pubmed":["38334129"],"doi":["10.1080/19420862.2024.2311991"]}}