[English] 日本語
Yorodumi Papers
- Database of articles cited by EMDB/PDB/SASBDB data -

+
Search query

Keywords
Structure methods
Author
Journal
IF

-
Structure paper

TitleStructural characterization of antibody-responses following Zolgensma treatment for AAV capsid engineering to expand patient cohorts.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 3731, Year 2025
Publish dateApr 19, 2025
AuthorsMario Mietzsch / Jane Hsi / Austin R Nelson / Neeta Khandekar / Ann-Maree Huang / Nicholas Jc Smith / Jon Zachary / Lindsay Potts / Michelle A Farrar / Paul Chipman / Mohammad Ghanem / Ian E Alexander / Grant J Logan / Juha T Huiskonen / Robert McKenna /
PubMed AbstractMonoclonal antibodies are useful tools to dissect the neutralizing antibody response against the adeno-associated virus (AAV) capsids that are used as gene therapy delivery vectors. The presence of ...Monoclonal antibodies are useful tools to dissect the neutralizing antibody response against the adeno-associated virus (AAV) capsids that are used as gene therapy delivery vectors. The presence of pre-existing neutralizing antibodies in large portions of the human population poses a significant challenge for AAV-mediated gene therapy, primarily targeting the capsid leading to vector inactivation and loss of treatment efficacy. This study structurally characterizes the interactions of 21 human-derived neutralizing antibodies from three patients treated with the AAV9 vector, Zolgensma®, utilizing high-resolution cryo-electron microscopy. The antibodies bound to the 2-fold depression or the 3-fold protrusions do not conform to the icosahedral symmetry of the capsid, thus requiring localized reconstructions. These complex structures provide unprecedented details of the mAbs binding interfaces, with many antibodies inducing structural perturbations of the capsid upon binding. Key surface capsid amino acid residues were identified facilitating the design of capsid variants with antibody escape phenotypes. These AAV9 capsid variants have the potential to expand the patient cohort to include those that were previously excluded due to their pre-existing neutralizing antibodies against the wtAAV9 capsid, and the possibly of further treatment to those requiring redosing.
External linksNat Commun / PubMed:40253479 / PubMed Central
MethodsEM (single particle)
Resolution2.18 - 3.73 Å
Structure data

EMDB-44271, PDB-9b6n:
Fab1-1 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 3.31 Å

EMDB-44272, PDB-9b6o:
Fab1-2 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 2.61 Å

EMDB-44273, PDB-9b6p:
Fab1-3 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 3.13 Å

EMDB-44274, PDB-9b6q:
Fab1-4 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 2.77 Å

EMDB-44275, PDB-9b6r:
Fab1-5 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 3.19 Å

EMDB-44276, PDB-9b6s:
Fab1-6 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 3.47 Å

EMDB-44277, PDB-9b6t:
Fab1-7 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 2.54 Å

EMDB-44314, PDB-9b7k:
Fab2-1 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 2.75 Å

EMDB-44315, PDB-9b7l:
Fab2-2 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 2.82 Å

EMDB-44316, PDB-9b7m:
Fab2-3 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 2.82 Å

EMDB-44317, PDB-9b7n:
Fab2-4 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 3.02 Å

EMDB-44318, PDB-9b7o:
Fab2-5 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 2.86 Å

EMDB-44319, PDB-9b7p:
Fab2-6 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 2.98 Å

EMDB-44320, PDB-9b7q:
Fab2-7 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 2.18 Å

EMDB-44321, PDB-9b7r:
Fab3-1 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 3.02 Å

EMDB-44322, PDB-9b7s:
Fab3-2 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 2.84 Å

EMDB-44323, PDB-9b7t:
Fab3-3 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 3.56 Å

EMDB-44324, PDB-9b7u:
Fab3-4 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 3.73 Å

EMDB-44325, PDB-9b7v:
Fab3-5 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 2.76 Å

EMDB-44326, PDB-9b7w:
Fab3-6 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 3.36 Å

EMDB-44327, PDB-9b7x:
Fab3-7 in complex with the capsid of Adeno-associated virus type 9
Method: EM (single particle) / Resolution: 2.76 Å

Chemicals

ChemComp-HOH:
WATER

ChemComp-CA:
Unknown entry

Source
  • adeno-associated virus
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Adeno-associated virus / AAV / capsid / Fab-complex / antibody / NAb / VIRUS / VIRAL PROTEIN-IMMUNE SYSTEM complex

+
About Yorodumi Papers

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242):Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi Papers

Database of articles cited by EMDB/PDB/SASBDB data

  • Database of articles cited by EMDB, PDB, and SASBDB entries
  • Using PubMed data

Related info.:EMDB / PDB / SASBDB / Yorodumi / EMN Papers / Changes in new EM Navigator and Yorodumi

Read more