Evidence map›Paper›PMID 41814652›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2026

SORT LNPs encapsulating Cas9 mRNA achieve efficient editing in skeletal muscle in a dystrophic mouse model.

Sukanya Iyer, Katelyn Daman, Yehui Sun, Amanda Tutto, Sarah E Holbrook, Anya T Joynt, Jing Yan, Prajakta Ambegaokar, Dongsheng Guo, Pengpeng Liu and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

22 authors.

Sukanya IyerDepartment of Molecular, Cell, and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA; Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Katelyn DamanDepartment of Neurology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA; Wellstone Muscular Dystrophy Program, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Yehui SunDepartment of Biomedical Engineering, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Amanda TuttoDepartment of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Sarah E HolbrookDepartment of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA; The Jackson Laboratory, Bar Harbor, ME 04609, USA; The University of Maine, Orono, ME 04469, USA.
Anya T JoyntDepartment of Molecular, Cell, and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Jing YanDepartment of Neurology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA; Wellstone Muscular Dystrophy Program, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Prajakta AmbegaokarDepartment of Molecular, Cell, and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Dongsheng GuoDepartment of Neurology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA; Wellstone Muscular Dystrophy Program, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Pengpeng LiuDepartment of Molecular, Cell, and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Jennifer E StaufferThe Jackson Laboratory, Bar Harbor, ME 04609, USA.
Stacy A MaitlandDepartment of Molecular, Cell, and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Sang M LeeDepartment of Biomedical Engineering, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Yufen XiaoDepartment of Biomedical Engineering, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Hsi-Chien HuangDepartment of Biomedical Engineering, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Lihua J ZhuDepartment of Molecular, Cell, and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Thomas L GallagherDepartment of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Gregory A CoxThe Jackson Laboratory, Bar Harbor, ME 04609, USA; The University of Maine, Orono, ME 04469, USA.
Allison M KeelerDepartment of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA; Li Weibo Institute for Rare Disease Research, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Daniel J SiegwartDepartment of Biomedical Engineering, Program in Genetic Drug Engineering, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: daniel.siegwart@utsouthwestern.edu.
Charles P EmersonDepartment of Neurology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA; Wellstone Muscular Dystrophy Program, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA; Li Weibo Institute for Rare Disease Research, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA. Electronic address: charles.emersonjr@umassmed.edu.
Scot A WolfeDepartment of Molecular, Cell, and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA; Li Weibo Institute for Rare Disease Research, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA. Electronic address: scot.wolfe@umassmed.edu.

Funding

Vector Immunology CoreP01HL158506 · NHLBI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Terence R. Flotte · 2021 to 2026
$19.5M
The HUSH complex in HIV-1 latencyR37AI147868 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI JEREMY LUBAN · 2019 to 2026
$6.4M
Rectifying splicing mutations in blood disorders by gene editingR01HL150669 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI BAUER, DANIEL EVAN, WOLFE, SCOT A · 2020 to 2023
$3.5M
Defining the molecular interactions within nanoparticles that enable delivery of long nucleic acidsR01EB025192 · NIBIB · UT SOUTHWESTERN MEDICAL CENTER · PI SIEGWART, DANIEL JOHN · 2018 to 2025
$3.1M
Enhancing CRISPR Gene Editing in Somatic Tissues by Chemical Modification of Guides and DonorsUH3TR002668 · NCATS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KHVOROVA, ANASTASIA, SONTHEIMER, ERIK J. · 2021 to 2022
$3.1M
Chemotherapy-free cure of hemoglobin disorders through base editingR01HL170629 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI Daniel Evan Bauer, Pietro Genovese · 2023 to 2026
$3.1M
Multiplexed nanoparticle delivery to increase CRISPR/Cas gene editing for enhanced cancer therapyR01CA269787 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Daniel John Siegwart · 2022 to 2026
$1.9M
NCATS NIH HHS UH3 TR002668NCI NIH HHS R01 CA269787NHLBI NIH HHS P01 HL158506NHLBI NIH HHS R01 HL150669NHLBI NIH HHS R01 HL170629NIAID NIH HHS R37 AI147868NIBIB NIH HHS R01 EB025192
6 · The paper itself

Abstract

Limb girdle muscular dystrophy (LGMD) is the fourth most common type of muscular dystrophy. Gene editing holds promise for treating neuromuscular disorders such as LGMD, but clinical translation remains challenging due to lack of complementary delivery tools for skeletal muscle. Lipid nanoparticles (LNPs) offer a promising platform for transient delivery of gene-editing reagents as mRNA or ribonucleoprotein complexes (RNPs) to skeletal muscle, but editing efficiencies remain modest. While lipid compositions have been optimized to improve delivery to muscle, the impact of cargo type on editing efficiency, biodistribution, and immune response has not been evaluated. Here, we demonstrate that selective organ targeting (SORT) LNPs encapsulating optimized Cas9 cargo facilitate efficient, local delivery to skeletal muscle. Using an LGMDR7 mouse model harboring a mutation in TCAP as a proof-of-concept target, we show that LNP cargo type impacts LNP size, delivery to neighboring muscle groups, and editing efficiency. RNP and mRNA LNPs also provoked distinct innate and adaptive immune responses upon repeated dosing. The optimized SORT LNP platform resulted in 40% restoration of Telethonin expression in treated muscle. Overall, these findings offer valuable insights for the continued development of LNP-based gene-editing reagents to facilitate disease-modifying interventions for neuromuscular diseases.

Indexed as

CRISPR-Associated Protein 9CRISPR-Cas SystemsGene EditingLipidsMuscle, SkeletalMuscular Dystrophies, Limb-GirdleNanoparticlesRNA, MessengerAnimalsDisease Models, AnimalGenetic TherapyLiposomesMiceCRISPR-Associated Protein 9Lipid NanoparticlesLipidsLiposomesRNA, MessengerCas9 nucleasein vivo editingLGMD2GLGMD mouse modelLGMDR7limb-girdle muscular dystrophylipid nanoparticlesLNP immunogenicityskeletal muscle deliverySORT LNPs

Identifiers

PMID41814652
PMCPMC13157202

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