Cited by 89Hemophilia Treatment and ResearchRNA Interference and Gene DeliveryVirus-based gene therapy research

Treatment of Hemophilia A Using Factor VIII Messenger RNA Lipid Nanoparticles

Open access
Chen, Chun-Yu, Tran, Dominic M., Cavedon, Alex, Cai, Xiaohe, Rajendran, Raj, Lyle, Meghan J., Martini, Paolo G.V., Miao, Carol H.·2020·Molecular Therapy Nucleic Acids

Abstract

Hemophilia A (HemA) patients are currently treated with costly and inconvenient replacement therapy of short-lived factor VIII (FVIII) protein. Development of lipid nanoparticle (LNP)-encapsulated mRNA encoding FVIII can change this paradigm. LNP technology constitutes a biocompatible and scalable system to efficiently package and deliver mRNA to the target site. Mice intravenously infused with the luciferase mRNA LNPs showed luminescence signals predominantly in the liver 4 h after injection. Repeated injections of LNPs did not induce elevation of liver transaminases. We next injected LNPs carrying mRNAs encoding different variants of human FVIII (F8 LNPs) into HemA mice. A single injection of B domain-deleted F8 LNPs using different dosing regimens achieved a wide range of therapeutic activities rapidly, which can be beneficial for various usages in hemophilia treatment. The expression slowly declined yet remained above therapeutic levels up to 5-7 days post-injection. Furthermore, routine repeated injections of F8 LNPs in immunodeficient mice produced consistent expression of FVIII over time. In conclusion, F8 LNP treatment produced rapid and prolonged duration of FVIII expression that could be applied to prophylactic treatment and potentially various other treatment options. Our study showed potential for a safe and effective platform of new mRNA therapies for HemA.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.omtn.2020.03.015

Cites

62 of 62 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • mRNA-based protein replacement therapies have been applied to haematological diseases, central nervous system disorders, skin diseases and hearing loss in preclinical studies.

    “In addition, mRNA-based protein replacement therapies have been applied to haematological diseases (for example, haemophilia A232, haemophilia B91,104,233 and thrombotic thrombocytopaenic purpura234), central nervous system disorders67,152 (for example, Friedreich’s ataxia67), skin diseases235,236 (for example, elastin deficiency235) and hearing loss237 in preclinical”

    From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [232]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Chen, C.-Y., Tran, D. M., Cavedon, A., Cai, X., Rajendran, R., Lyle, M. J., Martini, P. G. V., & Miao, C. H.
Affiliations
  • Seattle Children's Research Institute (US)
  • Moderna Therapeutics (United States) (US)
  • University of Washington (US)
Corresponding author
Miao, Carol H.
Venue
Molecular Therapy Nucleic Acids
Publisher
Elsevier BV
Published
2020-06
Volume
20
Pages
534-544
ISSN
2162-2531 (ISSN-L)
OpenAlex
W3015503845
Cited by
89
References
62
Citations by year
2026: 10 · 2025: 10 · 2024: 25 · 2023: 19 · 2022: 13 · 2021: 9 · 2020: 3
FWCI
6.95
Type
journal article
Language
en
Open access
Locations
  • Molecular Therapy — Nucleic Acids (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Moderna Therapeutics
Topics
  • Health Sciences › Medicine › Hematology › Hemophilia Treatment and Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Keywords
hemophilia A, factor VIII, lipid nanoparticle mRNA delivery, mRNA therapeutics, B-domain-deleted factor VIII, prophylaxis, immunodeficient mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review