Researchers engineered and characterized a blood-brain barrier transport vehicle targeting the CD98 heavy chain of heterodimeric amino acid transporters.
By Pooja Toshniwal PahariaAug 24 2023Reviewed by Sophia Coveney In a recent study published in Nature Communications, researchers engineered and characterized a blood-brain barrier transport vehicle targeting the CD98 heavy chain of heterodimeric amino acid transporters .
Cynomolgus monkeys and humanized CD98hc knock-in murine animals were used to test the pharmacokinetic and biodistribution features of a CD98hc antibody transport vehicle . After chronic treatment, the researchers assessed brain uptake, ATVCD98hc clearance, biodistribution in the CNS, and safety. Related StoriesTo determine whether additional binding may influence CD98hc-mediated biodistribution and retention, Fabs that targeted and inhibited the activities of beta-secretase 1 protein were incorporated in the mono- and bi-valent ATVCD98hc.6.39 structures. ATVCD98hc:BACE1 variations were introduced intravenously into CD98hcmu/hu knock-in murine animals, and serological and brain pharmacokinetics were assessed.
Results The clearance, uptake kinetics, and biodistribution features of ATVCD98hc molecules varied from those of the previously described ATVTfR. In comparison to other known Blood-brain-barrier platforms that targeted TfR, peripherally given ATVCD98hc displayed distinct brain delivery with much slower kinetic characteristics.
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