Evidence map›Paper›PMID 41555020›Full record

ArticleNature biotechnology2026

An engineered UGA suppressor tRNA gene for disease-agnostic AAV delivery.

Mengyao Xu, Hao Liu, Jiaming Wang, Andre F C Vieira, Xuntao Zhou, Nan Liu, Jialing Liang, Ailing Du, Xiupeng Chen, Ruxiao Xing and 4 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. 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

14 authors.

Mengyao Xu *Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Hao Liu *Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Jiaming WangDepartment of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-4834-967X
Andre F C VieiraDepartment of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0009-0008-4157-0145
Xuntao ZhouDepartment of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Nan LiuDepartment of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0009-0004-9557-6017
Jialing LiangDepartment of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Ailing DuDepartment of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Xiupeng ChenDepartment of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0001-5916-3953
Ruxiao XingDepartment of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Yang YangBorch Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN, USA.ORCID http://orcid.org/0000-0001-6417-3654
Maria P Gonzalez-PerezDepartment of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0001-7354-367X
Vikas KumarDepartment of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Dan WangDepartment of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA. Dan.Wang@umassmed.edu.ORCID http://orcid.org/0000-0001-9079-2360

Funding

Vector Immunology CoreP01HL158506 · NHLBI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Terence R. Flotte · 2021 to 2026
$19.5M
NHLBI NIH HHS P01 HL158506UMASS | University of Massachusetts Medical School (UMass Medical School) UMass Chan BRIDGE Fund AwardU.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) P01HL158506
6 · The paper itself

Abstract

Suppressor transfer RNAs (sup-tRNAs) have the potential to rescue nonsense mutations in a disease-agnostic manner and are an alternative therapeutic approach for many rare and ultrarare disorders. Among all human pathogenic nonsense variants, approximately 20% arise from C-to-T transitions that convert the CGA arginine codon into a UGA stop codon. While recombinant adeno-associated virus (rAAV) has been successfully used to deliver a UAG-targeting sup-tRNA gene in vivo, extending this approach to UGA-targeting sup-tRNA genes has posed unique challenges related to rAAV vector production. Here, we demonstrate that an engineered UGA-sup-tRNA gene, designed with transcriptional regulatory elements, can be efficiently packaged into rAAV for in vivo delivery. A single administration in mouse models of two distinct lysosomal storage disorders restores enzymatic activity to approximately 10% of normal levels. Comparative analysis reveals differential sup-tRNA expression and aminoacylation patterns across tissue types, which correlate with enhanced therapeutic effects. The applied rAAV-based agents and engineering strategies expand the potential therapeutic scope of sup-tRNA therapies.

Identifiers

PMID41555020

What OpenQuestion holds

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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.