Evidence map›Paper›PMID 36748274›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023

Cholesterol-Amino-Phosphate (CAP) Derived Lipid Nanoparticles for Delivery of Self-Amplifying RNA and Restoration of Spermatogenesis in Infertile Mice.

Shi Du, Wenqing Li, Yuebao Zhang, Yonger Xue, Xucheng Hou, Jingyue Yan, Jeffrey Cheng, Binbin Deng, David W McComb, Jennifer Lin and 5 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
8.2field-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

30 citing papers in PubMed, 53 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Testicular mRNA-LNP Delivery: A Novel Therapy for Genetic Spermatogenic Disorders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  5. Article
  6. Review
  7. Review
  8. Restoring fertility with a lipid nanoparticle-mRNA platform: A new era in male germline therapy.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Article
  10. Sperm and offspring production in a nonobstructive azoospermia mouse model via testicular mRNA delivery using lipid nanoparticles.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Enhancing RNA-lipid nanoparticle delivery: Organ- and cell-specificity and barcoding strategies.Journal of controlled release : official journal of the Controlled Release Society · 2024
    Review
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 2 countries.

Shi DuDivision of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA.
Wenqing LiDivision of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA.
Yuebao ZhangDivision of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA.
Yonger XueDivision of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA.
Xucheng HouDivision of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA.
Jingyue YanDivision of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA.
Jeffrey ChengDivision of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA.
Binbin DengCenter for Electron Microscopy and Analysis, The Ohio State University, Columbus, OH, 43212, USA.
David W McCombCenter for Electron Microscopy and Analysis, The Ohio State University, Columbus, OH, 43212, USA.
Jennifer LinTransgenic, Knockout, and Tumor Model Center, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Hong ZengTransgenic, Knockout, and Tumor Model Center, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Xiaolin ChengDivision of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA.
Darrell J IrvineDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Ron WeissDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Yizhou DongDivision of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA.ORCID 0000-0001-5786-0659
The Ohio State University · USStanford University · USAllen Institute for Brain Science · USHoward Hughes Medical Institute · USMassachusetts Institute of Technology · US

Funding

Construction of in vivo mRNA delivery systemsR35GM144117 · NIGMS · OHIO STATE UNIVERSITY · PI Yizhou Dong · 2022 to 2026
$2.4M
Cell-specific and multifunctional drug formulations for in vivo deliveryR35GM119679 · NIGMS · OHIO STATE UNIVERSITY · PI DONG, YIZHOU · 2016 to 2020
$1.9M
Maximizing Investigators' Research Award R35GM119679Maximizing Investigators' Research Award R35GM144117NIGMS NIH HHSNIGMS NIH HHS R35 GM119679NIGMS NIH HHS R35 GM144117
6 · The paper itself

Abstract

Male infertility caused by genetic mutations is an important type of infertility. Currently, there is no reliable method in the clinic to address this medical need. The emergence of mRNA therapy provides a possible strategy for restoring mutant genes in the reproductive system. However, effective delivery of mRNA to spermatocytes remains a formidable challenge. Here a series of cholesterol-amino-phosphate (CAP) lipids are reported by integrating three bioactive moieties into a geometric structure, which is favorable for mRNA delivery. The results demonstrate that CAP-derived lipid nanoparticles (CAP LNPs) can deliver RNA including traditional mRNA and self-amplifying RNA (saRNA) encoding DNA Meiotic Recombinase 1 (Dmc1) protein in spermatocytes and treat male infertility caused by the Dmc1 gene mutation. Notably, the delivery efficiency of CAP LNPs is significantly higher than that of the MC3 and ALC-0315 LNPs, which is consistent with the design of CAP molecules. More importantly, a single injection of CAP LNPs-saRNA can produce Dmc1 protein for an extended period, which restores the spermatogenesis in the Dmc1 gene knockout mouse model. Overall, this study proves the concept of LNPs for the delivery of mRNA to spermatocytes, which provides a unique method to probe male infertility caused by the genetic mutation.

Indexed as

Infertility, MaleRNAAnimalsCholesterolHumansLiposomesMaleMiceNanoparticlesRNA, MessengerSpermatogenesisCholesterolLipid NanoparticlesLiposomesRNARNA, Messengerlipid nanoparticlesmale infertilitymRNA therapyself-amplifying RNAspermatocytes delivery

Identifiers

PMID36748274
PMCPMC10104632
OpenAlexW4319334267

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.