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- W2896685834 abstract "Antibody, immuno- and gene therapies developed for neurological indications face a delivery challenge posed by various anatomical and physiological barriers within the central nervous system (CNS); most notably, the blood–brain barrier (BBB). Emerging delivery technologies for biotherapeutics have focused on trans-cellular pathways across the BBB utilizing receptor-mediated transcytosis (RMT). ‘Traditionally’ targeted RMT receptors, transferrin receptor (TfR) and insulin receptor (IR), are ubiquitously expressed and pose numerous translational challenges during development, including species differences and safety risks. Recent advances in antibody engineering technologies and discoveries of RMT targets and BBB-crossing antibodies that are more BBB-selective have combined to create a new preclinical pipeline of BBB-crossing biotherapeutics with improved efficacy and safety. Novel BBB-selective RMT targets and carrier antibodies have exposed additional opportunities for re-targeting gene delivery vectors or nanocarriers for more efficient brain delivery. Emergence and refinement of core technologies of genetic engineering and editing as well as biomanufacturing of viral vectors and cell-derived products have de-risked the path to the development of systemic gene therapy approaches for the CNS. In particular, brain-tropic viral vectors and extracellular vesicles have recently expanded the repertoire of brain delivery strategies for biotherapeutics. Whereas protein biotherapeutics and bispecific antibodies enabled for BBB transcytosis are rapidly heading towards clinical trials, systemic gene therapy approaches for CNS will likely remain in research phase for the foreseeable future. The promise and limitations of these emerging cross-BBB delivery technologies are further discussed in this article." @default.
- W2896685834 created "2018-10-26" @default.
- W2896685834 creator A5043006925 @default.
- W2896685834 creator A5077677223 @default.
- W2896685834 creator A5082512370 @default.
- W2896685834 date "2018-10-10" @default.
- W2896685834 modified "2023-10-12" @default.
- W2896685834 title "Emerging Technologies for Delivery of Biotherapeutics and Gene Therapy Across the Blood–Brain Barrier" @default.
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