IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-08852-4.html
   My bibliography  Save this article

Intradermal delivery of modified mRNA encoding VEGF-A in patients with type 2 diabetes

Author

Listed:
  • Li-Ming Gan

    (AstraZeneca Gothenburg
    Sahlgrenska Academy at the University of Gothenburg
    Sahlgrenska University Hospital)

  • Maria Lagerström-Fermér

    (AstraZeneca Gothenburg)

  • Leif G. Carlsson

    (AstraZeneca Gothenburg)

  • Cecilia Arfvidsson

    (AstraZeneca Gothenburg)

  • Ann-Charlotte Egnell

    (AstraZeneca Gothenburg)

  • Anna Rudvik

    (AstraZeneca Gothenburg)

  • Magnus Kjaer

    (AstraZeneca Gothenburg)

  • Anna Collén

    (AstraZeneca Gothenburg)

  • James D. Thompson

    (Moderna, Inc., 200 Technology Square)

  • John Joyal

    (Moderna, Inc., 200 Technology Square)

  • Ligia Chialda

    (PAREXEL Early Phase Clinical Unit, Westend Clinic, House 31)

  • Thomas Koernicke

    (PAREXEL Early Phase Clinical Unit, Westend Clinic, House 31)

  • Rainard Fuhr

    (PAREXEL Early Phase Clinical Unit, Westend Clinic, House 31)

  • Kenneth R. Chien

    (Karolinska Institutet
    Karolinska Institutet)

  • Regina Fritsche-Danielson

    (AstraZeneca Gothenburg)

Abstract

Chemically modified mRNA is an efficient, biocompatible modality for therapeutic protein expression. We report a first-time-in-human study of this modality, aiming to evaluate safety and potential therapeutic effects. Men with type 2 diabetes mellitus (T2DM) received intradermal injections of modified mRNA encoding vascular endothelial growth factor A (VEGF-A) or buffered saline placebo (ethical obligations precluded use of a non-translatable mRNA control) at randomized sites on the forearm. The only causally treatment-related adverse events were mild injection-site reactions. Skin microdialysis revealed elevated VEGF-A protein levels at mRNA-treated sites versus placebo-treated sites from about 4–24 hours post-administration. Enhancements in basal skin blood flow at 4 hours and 7 days post-administration were detected using laser Doppler fluximetry and imaging. Intradermal VEGF-A mRNA was well tolerated and led to local functional VEGF-A protein expression and transient skin blood flow enhancement in men with T2DM. VEGF-A mRNA may have therapeutic potential for regenerative angiogenesis.

Suggested Citation

  • Li-Ming Gan & Maria Lagerström-Fermér & Leif G. Carlsson & Cecilia Arfvidsson & Ann-Charlotte Egnell & Anna Rudvik & Magnus Kjaer & Anna Collén & James D. Thompson & John Joyal & Ligia Chialda & Thoma, 2019. "Intradermal delivery of modified mRNA encoding VEGF-A in patients with type 2 diabetes," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08852-4
    DOI: 10.1038/s41467-019-08852-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-08852-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-08852-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08852-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.