Evidence map›Paper›PMID 42774508›Full record

ArticleiScience2026

Construction of a self-amplifying mRNA-LNP complex for phenylalanine hydroxylase and its efficacy evaluation in gene therapy for phenylketonuria.

Ziqi Wen, Yiling Long, Wenjing Shi, Wenjing Song, Rongjun Xu, Xingri Zhan, Xiuyuan Wang, Rui Su, Yu Wang, Jia Fei

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Ziqi WenState Key Laboratory of Bioactive Molecules and Druggability Assessment, Department of Biochemistry and Molecular Biology, Medical College of Jinan University, Guangzhou 510632, China.
Yiling LongState Key Laboratory of Bioactive Molecules and Druggability Assessment, Department of Biochemistry and Molecular Biology, Medical College of Jinan University, Guangzhou 510632, China.
Wenjing ShiState Key Laboratory of Bioactive Molecules and Druggability Assessment, Department of Biochemistry and Molecular Biology, Medical College of Jinan University, Guangzhou 510632, China.
Wenjing SongState Key Laboratory of Bioactive Molecules and Druggability Assessment, Department of Biochemistry and Molecular Biology, Medical College of Jinan University, Guangzhou 510632, China.
Rongjun XuState Key Laboratory of Bioactive Molecules and Druggability Assessment, Department of Biochemistry and Molecular Biology, Medical College of Jinan University, Guangzhou 510632, China.
Xingri ZhanState Key Laboratory of Bioactive Molecules and Druggability Assessment, Department of Biochemistry and Molecular Biology, Medical College of Jinan University, Guangzhou 510632, China.
Xiuyuan WangState Key Laboratory of Bioactive Molecules and Druggability Assessment, Department of Biochemistry and Molecular Biology, Medical College of Jinan University, Guangzhou 510632, China.
Rui SuState Key Laboratory of Bioactive Molecules and Druggability Assessment, Department of Biochemistry and Molecular Biology, Medical College of Jinan University, Guangzhou 510632, China.
Yu WangDepartment of endocrinology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Jia FeiState Key Laboratory of Bioactive Molecules and Druggability Assessment, Department of Biochemistry and Molecular Biology, Medical College of Jinan University, Guangzhou 510632, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Phenylketonuria (PKU) is an autosomal recessive disorder caused by deficient phenylalanine hydroxylase (PAH) activity, with current pharmacotherapies showing limited response rates and age-dependent restrictions. We compared two liver-targeted lipid nanoparticle formulations delivering PAH-encoding mRNA-a self-amplifying construct (saRNA) and a conventional non-replicating counterpart (nr-mRNA)-in Pah-knockout mice. Both constructs reduced circulating phenylalanine (Phe) after a single intravenous injection. The saRNA formulation achieved comparable efficacy at one-sixth the nr-mRNA dose and maintained physiological Phe levels for 14 days, whereas nr-mRNA produced only transient reductions. Repeated saRNA administration was well tolerated, with no detectable immunogenicity or hepatic toxicity. These results establish that saRNA-mediated PAH replacement provides sustained activity with substantial dose reduction, overcoming the short-lived effect of non-replicating mRNA. This platform may inform broader strategies for durable enzyme therapy in inherited metabolic diseases requiring liver-restored function.

Indexed as

lipid nanoparticleLNPmRNA technologyphenylketonuriaPKUreplacement therapyself-amplifying mRNA

Identifiers

PMID42774508
PMCPMC13594751

What OpenQuestion holds

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Registered trials

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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.