Evidence map›Paper›PMID 38399714›Full record

ArticleMicroorganisms2024

A Comprehensive Study of the Effects by Sequence Truncation within Inverted Terminal Repeats (ITRs) on the Productivity, Genome Packaging, and Potency of AAV Vectors.

Yinxing Chen, Shiliang Hu, William Lee, Noel Walsh, Kayla Iozza, Neil Huang, Gregory Preston, Lauren M Drouin, Nannan Jia, June Deng and 2 more

Open access · goldAbstract read
In one paragraph

Article in Microorganisms, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
7.2field-weighted citation impact, top 3% 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

13 citing papers in PubMed, 13 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

12 authors at 1 institution in 1 country.

Yinxing ChenGenomic Medicine, Alexion, AstraZeneca Rare Disease, 65 Hayden Avenue, Lexington, MA 02421, USA.
Shiliang HuGenomic Medicine, Alexion, AstraZeneca Rare Disease, 65 Hayden Avenue, Lexington, MA 02421, USA.
William LeeGenomic Medicine, Alexion, AstraZeneca Rare Disease, 65 Hayden Avenue, Lexington, MA 02421, USA.
Noel WalshGenomic Medicine, Alexion, AstraZeneca Rare Disease, 65 Hayden Avenue, Lexington, MA 02421, USA.
Kayla IozzaGenomic Medicine, Alexion, AstraZeneca Rare Disease, 65 Hayden Avenue, Lexington, MA 02421, USA.
Neil HuangGenomic Medicine, Alexion, AstraZeneca Rare Disease, 65 Hayden Avenue, Lexington, MA 02421, USA.
Gregory PrestonGenomic Medicine, Alexion, AstraZeneca Rare Disease, 65 Hayden Avenue, Lexington, MA 02421, USA.
Lauren M DrouinGenomic Medicine, Alexion, AstraZeneca Rare Disease, 65 Hayden Avenue, Lexington, MA 02421, USA.
Nannan JiaGenomic Medicine, Alexion, AstraZeneca Rare Disease, 65 Hayden Avenue, Lexington, MA 02421, USA.
June DengGenomic Medicine, Alexion, AstraZeneca Rare Disease, 65 Hayden Avenue, Lexington, MA 02421, USA.
Matthias HebbenGenomic Medicine, Alexion, AstraZeneca Rare Disease, 65 Hayden Avenue, Lexington, MA 02421, USA.ORCID 0000-0002-2684-1153
Jing LiaoGenomic Medicine, Alexion, AstraZeneca Rare Disease, 65 Hayden Avenue, Lexington, MA 02421, USA.
Alexion Pharmaceuticals (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

One of the primary challenges in working with adeno-associated virus (AAV) lies in the inherent instability of its inverted terminal repeats (ITRs), which play vital roles in AAV replication, encapsidation, and genome integration. ITRs contain a high GC content and palindromic structure, which occasionally results in truncations and mutations during plasmid amplification in bacterial cells. However, there is no thorough study on how these alterations in ITRs impact the ultimate AAV vector characteristics. To close this gap, we designed ITRs with common variations, including a single B, C, or D region deletion at one end, and dual deletions at both ends of the vector genome. These engineered ITR-carrying plasmids were utilized to generate AAV vectors in HEK293 cells. The crude and purified AAV samples were collected and analyzed for yield, capsid DNA-filled percentage, potency, and ITR integrity. The results show that a single deletion had minor impact on AAV productivity, packaging efficiency, and in vivo potency. However, deletions on both ends, except A, showed significant negative effects on the above characteristics. Our work revealed the role of ITR regions, A, B, C, and D for AAV production and DNA replication, and proposes a new strategy for the quality control of ITR-bearing plasmids and final AAV products.

Indexed as

ITRsnanopore sequencingpackagingpotencyproductivityrAAV

Identifiers

PMID38399714
PMCPMC10892565
OpenAlexW4391450380

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.