1. 1868

    Friedrich Miescher discovers nucleic acids (´nuclein´) in Tübingen. Four years later he also discovers protamine

  2. 1953

    The discovery of the double-helix structure of DNA by James Watson and Francis Crick leads to ground-breaking insights into the genetic code and protein synthesis.

  3. 1956

    The scientists Elliot Volkin and Lazarus Astrachan of Oak Ridge National Laboratory (ORNL) in Tennessee discover the so-called "DNA-like-RNA".

  4. 1960

    François Jacob and Jacques Monod conduct their famous study of the control of expression of genes in the lac operon and provide the first example of a transcriptional regulation system. They name it "messenger RNA" (mRNA).

  5. 1965

    Robert Holley describes the structure of alanine transfer RNA and links DNA and protein synthesis. He shares the Nobel Prize with Har Gobind Khorana and Marshall Warren Nirenberg.

  6. 1969

    Devin Absher and colleagues show that double-stranded RNA has immunostimulatory properties; this is the initial evidence that double-stranded RNA could potentially have a place in the vaccine area. There are no data shown on single-stranded mRNA.

  7. 1977

    RNA splicing and introns are discovered by Philip Sharp and Richard Roberts, who win the Noble Prize for this research.

  8. 1990

    Wolff and colleagues describe gene transfer of mRNA into mice and achieve gene expression for a variety of proteins after direct injection of the corresponding mRNA into the muscles of mice.

  9. 1993

    The first preclinical data featuring mRNA-based vaccinations are published by F. Martinon and colleagues.

  10. 2000

    Ingmar Hoerr and colleagues publish the paper in which immunization experiments using naked mRNA as a control were discussed. Under the assumption that the unprotected RNA would be degraded during the experiment it was thought that RNA would be impossible to use as a vaccine. Astonishingly, RNA is able to cause a strong specific T-cell immune response. This publication leads to the foundation of CureVac.

  11. 2003

    First direct mRNA treatment (library immunization) worldwide administered at the University of Tübingen. The mRNA from CureVac is given to a cancer patient.

  12. 2004

    Sirna initiates first phase I trial of siRNA-based treatment for age-related macular degeneration.

  13. 2005

    Viral RNA is applied as ´foreign´ nucleic acids, and this stimulates the mammalian innate immune system - the non-specific immune system - through activation of Toll-like receptors (TLRs)
    (Diebold et al., 2004; Heil et al., 2004,); the innate immune system detects RNA lacking nucleoside modifications (Kariko et al., 2005).

  14. 2006

    Andrew Z. Fire and Craig C. Mello win the Nobel Prize for their discovery of RNA interference - gene silencing by double-stranded RNA.

    CureVac achieves authorization for the first GMP manufacturing facility to produce large single-stranded RNA molecules for medical purposes.

  15. 2008

    Denmark‘s Santaris initiates a phase I study of SPC3649, a potential treatment for hepatitis C. The trial marks the first time a microRNA drug has been tested in humans.

    CureVac starts worldwide the first clinical trial with an mRNA-based cancer immunotherapy (RNActive®); it is a phase I/IIa study with prostate cancer patients.

  16. 2009

    CureVac gets approval for its phase I/IIa study in lung cancer and FDA approval for phase I/IIa study in prostate cancer.

  17. 2011

    CureVac presents positive phase I/IIa data from prostate and lung cancer trials; both trials show biological activity of mRNA-based cancer immunotherapies.

  18. 2012

    Preclinical experiments with pseudouridinecontaining mRNA encoding erythropoietin (EPO) result in levels of functional EPO and a significant increase of both reticulocyte counts and hematocrits demonstrating the great potential for clinical applications of therapeutic mRNA (Kariko et al, 2012).

    Data published in Nature Biotechnology by the Friedrich-Loeffler-Institute (FLI) and CureVac demonstrate that mRNA-based prophylactic vaccines (RNActive®) have the potential to provide an effective protection against infectious diseases; data show that the mRNA vaccines induce balanced, long-lived and protective immunity to influenza A infections in various animal models.

  19. 2013

    CureVac completes recruitment of a phase IIb trial of mRNA-based cancer immunotherapy (RNActive® CV9103/9104) in 197 patients with castration-resistant prostate cancer.

    Combination of mRNA-based cancer immunotherapy and radiotherapy is tested by CureVac in an explorative phase I study.

    CureVac starts first phase I study with healthy volunteers to test RNActive® prophylactic vaccine against rabies.

    The 1st International mRNA Health Conference, hosted by the University of Tübingen, The University Hospital of Tübingen and CureVac, brings together more than 150 mRNA experts from all over the world and lays the foundation for the new biotechnological sector of mRNA-based therapeutics.

  20. 2014

    CureVac wins the 2 Mio. EUR Vaccine Prize from the EU for its innovative vaccine technology RNActive®.

    The Bill & Melinda Gates Foundation enters into a partnership with CureVac for the development of mRNA-based vaccines against infectious diseases which have an enormous impact on global health.

    Sanofi Pasteur signs the first exclusive license agreement with CureVac to develop and commercialize an mRNA-based RNActive® vaccine against an undisclosed pathogen.

    Boehringer Ingelheim acquires from CureVac exclusive rights for the clinical development and commercialization of the lung cancer immunotherapy CV9202.

    The 2nd International mRNA Health Conference takes place - in the two-day event in Boston almost 300 attendees discuss the tremendous medical potential of mRNA for many therapeutic options.

  21. 2015

    The Bill & Melinda Gates Foundation invests in CureVac and funds three programs to develop prophylactic vaccines against infectious diseases that have a disproportionate impact on the world’s poorest countries.

    For the first time worldwide, CureVac publishes clinical data from a phase I/IIa trial with an mRNA-based cancer immunotherapy. The data indicate that CureVac’s product was well tolerated and immunogenic.

    In November, the old laboratory in the castle of Hohentübingen, Tübingen, Germany, where Friedrich Miescher discovered the nuclein acids DNA and RNA in 1869, was opened as biochemical museum. The so called “Cradle of Biochemistry” is said to be one of the first biochemical laboratories in the world.

  22. 2016

    CureVac starts the construction of a GMP facility in industrial size in order to enable worldwide market supply with RNA-based products in the future.

To be continued ...

Scientific
RNA Milestones

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