Authors
Yasunori Matsuzaki, Ayumu Konno, Kenji Sakamoto, Yasuo Uchida, Tetsuya Terasaki, Hirokazu Hirai
Published in
Molecular therapy. Advances. Volume 34. Issue 3. Pages 201783. Sep 10, 2026. Epub Jun 16, 2026.
Abstract
Recent advances in engineering adeno-associated virus (AAV) capsids capable of crossing the blood-brain barrier (BBB) have led to the development of numerous variants aimed at enhancing central nervous system gene delivery. Over the past decade, as new BBB-penetrant capsids were reported or independently identified through our own capsid library screening, we systematically evaluated their performance in adult marmosets, using a standardized experimental framework. Here, we present a cross-comparison of eleven AAV variants, predominantly AAV9-derived, alongside native AAV9 following systemic administration. Whole-brain reporter expression was quantitatively assessed using uniform imaging and analysis pipelines to enable relative comparison across animals. Under these conditions, most previously reported and newly identified BBB-penetrant variants-including those obtained through our own screening efforts-did not exhibit brain transduction levels clearly distinguishable from those of AAV9 based on whole-brain fluorescence intensity. In contrast, VCAP-102 consistently produced markedly higher brain-wide reporter expression across animals, accompanied by substantially increased vector genome copy numbers in the marmoset cortex, with most GFP-positive cells corresponding to neurons. These findings provide a systematic benchmark for evaluating BBB-penetrant AAV capsids in non-human primates and identify VCAP-102 as a highly efficient vector for systemic brain gene delivery.
PMID:
42405181
Bibliographic data and abstract were imported from PubMed on 06 Jul 2026.
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