9NRP

The AAVpo.6 capsid

これはPDB形式変換不可エントリーです。

9NRP の概要

• エントリーDOI: 10.2210/pdb9nrp/pdb
• EMDBエントリー: 49739
• 分子名称: Capsid protein VP1 (1 entity in total)
• 機能のキーワード: aavpo.6, porcine adeno-associated virus, gene therapy, vector, cryo-em, virus
• 由来する生物種: Adeno-associated virus
• タンパク質・核酸の鎖数: 60
• 化学式量合計: 3560966.94

構造登録者

Nelson, A.,Mietzsch, M.,McKenna, R. (登録日: 2025-03-14, 公開日: 2025-10-08)

主引用文献

Nelson, A.,Mietzsch, M.,Hsi, J.,Eby, J.,Chipman, P.,McKenna, R.
Structural and Functional Characterization of Porcine Adeno-Associated Viruses.
Viruses, 17:-, 2025

PubMed Abstract: Current gene therapy treatments utilizing adeno-associated virus (AAV) vectors are based on capsids of primate origin. However, pre-existing neutralizing anti-AAV antibodies, that are present in a significant portion of the population, can lead to vector inactivation and reduced therapeutic efficacy. Advances in DNA sequencing have facilitated the discovery of many AAVs from non-primate species, including isolates from pigs, which exhibit up to 50% capsid protein sequence divergence, compared to primate AAV serotypes. In this study, AAVs isolated from porcine tissues (AAVpo.1 and AAVpo.6) were selected for structural characterization due to their low capsid protein VP1 sequence identity compared to each other and to AAV9. The AAV vectors were produced via the standard triple transfection system in HEK293 cells using AAV2 to package AAV2-ITR vector genomes and were purified by iodixanol density gradient ultracentrifugation. The capsid structures of AAVpo.1 and AAVpo.6 were determined using cryo-electron microscopy and then compared to each other in addition to the AAV5 and AAV9 structures. Given that porcine AAVpo.6 has been reported to infect human cells and the ability to cross the blood-brain barrier, the functional characterization was focused on the identification of a potential glycan receptor utilized by the porcine capsids. Additionally, the porcine AAV capsid reactivity to human derived anti-AAV antibodies was assessed to evaluate the potential for these capsids to be used as alternative vectors for gene therapy, particularly for patients with pre-existing immunity to primate-derived AAV serotypes.

PubMed: 41012686
DOI: 10.3390/v17091260

実験手法

ELECTRON MICROSCOPY (1.77 Å)