Evidence map›Paper›PMID 37868210›Full record

ArticleMolecular therapy. Methods & clinical development2023

Adeno-associated viral capsid stability on anion exchange chromatography column and its impact on empty and full capsid separation.

Ohnmar Khanal, Vijesh Kumar, Mi Jin

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Methods & clinical development, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
9.7field-weighted citation impact, top 2% 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

15 citing papers in PubMed, 31 citations in OpenAlex.

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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

3 authors at 1 institution in 1 country.

Ohnmar KhanalTechnology Development, Spark Therapeutics, Inc., Philadelphia, PA, USA.
Vijesh KumarTechnology Development, Spark Therapeutics, Inc., Philadelphia, PA, USA.
Mi JinTechnology Development, Spark Therapeutics, Inc., Philadelphia, PA, USA.
Spark Therapeutics (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recombinant adeno-associated viral vector (rAAV) mediated gene therapy is gaining traction in treating genetic disorders. Current rAAV production systems yield a mixture of capsids largely devoid of the transgene (empty capsid) compared with the desired therapeutic product (full capsid). Anion exchange chromatography (AEX) is an attractive method for separating empty and full AAV capsids because of its scalability. Resin types and buffer composition are key considerations for AEX and must support capsid stability to be suitable for downstream processing. We examined the impact of binding durations (0-8 h) using various binding ionic strengths (15-75 mM), pH (7.5-9.0), resin chemistry (POROS XQ, POROS HQ, POROS I, and BIA QA monolith), and proprietary Q resins with different ligand densities for effects on capsid stability. Empty capsids were altered upon extended binding, leading to retention time shifts and loss of resolution between empty and full capsids. Viral capsid protein analysis reveals that full capsids have more viral capsid protein 3 (VP3) proteins than empty capsids. Analytical hydrophilic liquid chromatography showed that empty capsid retention time shift is accompanied by changes to the empty capsid's native VP3 protein. Among the potential stabilizing additives considered, magnesium chloride was the most effective at reducing negative impacts caused by extended binding.

Indexed as

AAV stabilityAEXanalytical hydrophilic interaction liquid chromatographyanion exchange chromatographyempty capsidsfull capsidsstability in adsorbed stateviral capsid proteins

Identifiers

PMID37868210
PMCPMC10585339
OpenAlexW4386865709

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.