Evidence map›Paper›PMID 33145372›Full record

ArticleMolecular therapy. Methods & clinical development2020

Characterization of AAV-Specific Affinity Ligands: Consequences for Vector Purification and Development Strategies.

Mario Mietzsch, J Kennon Smith, Jennifer C Yu, Vibhu Banala, Shanan N Emmanuel, Ariana Jose, Paul Chipman, Nilakshee Bhattacharya, Robert McKenna, Mavis Agbandje-McKenna

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Methods & clinical development, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
5.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 63 citations in OpenAlex.

  1. Article
  2. Structural basis of liver de-targeting and neuronal tropism of CNS-targeted AAV capsids.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  3. Article
  4. Article
  5. The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025
    Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Recombinant AAV Purification.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Mario MietzschDepartment of Biochemistry and Molecular Biology, Center for Structural Biology, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL, USA.
J Kennon SmithDepartment of Biochemistry and Molecular Biology, Center for Structural Biology, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL, USA.
Jennifer C YuDepartment of Biochemistry and Molecular Biology, Center for Structural Biology, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL, USA.
Vibhu BanalaDepartment of Biochemistry and Molecular Biology, Center for Structural Biology, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL, USA.
Shanan N EmmanuelDepartment of Biochemistry and Molecular Biology, Center for Structural Biology, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL, USA.
Ariana JoseDepartment of Biochemistry and Molecular Biology, Center for Structural Biology, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL, USA.
Paul ChipmanDepartment of Biochemistry and Molecular Biology, Center for Structural Biology, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL, USA.
Nilakshee BhattacharyaBiological Science Imaging Resource, Department of Biological Sciences, Florida State University, Tallahassee, FL, USA.
Robert McKennaDepartment of Biochemistry and Molecular Biology, Center for Structural Biology, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL, USA.
Mavis Agbandje-McKennaDepartment of Biochemistry and Molecular Biology, Center for Structural Biology, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL, USA.
University of Florida · USFlorida State University · US

Funding

Structural studies of AAV capsids and their glycan receptor interactionsR01GM082946 · NIGMS · UNIVERSITY OF FLORIDA · PI ROBERT MCKENNA · 2007 to 2026
$6.1M
BASIC MICROBIOLOGY &INFECTIOUS DISEASEST32AI007110 · NIAID · UNIVERSITY OF FLORIDA · PI Stephanie M Karst · 1985 to 2026
$4.3M
NIAID NIH HHS T32 AI007110NIGMS NIH HHS R01 GM082946
6 · The paper itself

Abstract

Affinity-based purification of adeno-associated virus (AAV) vectors has replaced density-based methods for vectors used in clinical settings. This method utilizes camelid single-domain antibodies recognizing AAV capsids. These include AVB Sepharose (AVB) and POROS CaptureSelect affinity ligand for AAV8 (CSAL8) and AAV9 (CSAL9). In this study, we utilized cryo-electron microscopy and 3D image reconstruction to map the binding sites of these affinity ligands on the capsids of several AAV serotypes, including AAV1, AAV2, AAV5, AAV8, and AAV9, representing the range of sequence and structure diversity among AAVs. The AAV-ligand complex structures showed that AVB and CSAL9 bound to the 5-fold capsid region, although in different orientations, and CSAL8 bound to the side of the 3-fold protrusion. The AAV contact residues required for ligand binding, and thus AAV purification, and the ability of the ligands to neutralize infection were analyzed. The data show that only a few residues within the epitopes served to block affinity ligand binding. Neutralization was observed for AAV1 and AAV5 with AVB, for AAV1 with CSAL8, and for AAV9 with CSAL9, associated with regions that overlap with epitopes for neutralizing monoclonal antibodies against these capsids. This information is critical and could be generally applicable in the development of novel AAV vectors amenable to affinity column purification.

Indexed as

adeno-associated virus (AAV)affinity chromatographycryo-electron microscopy and image reconstructionempty/full ratiogene therapynanobodiesneutralizing epitopesvector purification

Identifiers

PMID33145372
PMCPMC7591348
OpenAlexW3089792287

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.