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Nucleic Acid–Based Vaccines in Development for SARS-CoV-2

Posted on May 1st, 2020 by in COVID-19

With the coronavirus disease 2019 (COVID-19) case and death count climbing [1] despite multiple industry shutdowns and extensive social distancing efforts, it has become clear that a vaccine is required to control the spread of the COVID-19 causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many different researchers, institutes and companies specializing in vaccine development across the world have entered the race and announced a candidate, resulting in an astonishingly large number (>70) of vaccines in the pipeline [2,3].

This post discusses the nucleic acid vaccine candidates being tested, and a future post will discuss the other SARS-CoV-2 vaccine candidates (predominantly virus vectors and protein-based vaccines).

Many are advocating for a nucleic acid­–based vaccine to win the SARS-CoV-2 vaccine race. As of yet, no RNA or DNA vaccine has been approved for human use, but the technology has been improving over the past few years, and multiple DNA vaccines have been approved for use in animals [4].

Perfecting the RNA and DNA vaccine development strategy will be an important innovation going forward. With the extent of globalization and the increased frequency of epidemic and pandemic scares, vaccine development needs to occur much faster (than the average 10 years [5]) to protect us from highly transmittable infectious pathogens. RNA and DNA vaccines provide us the potential for more rapid vaccine development because synthetic RNA and DNA are easier to construct and purify from contaminants (improving safety) and scale up to large volume than traditional vaccines.

Because we are in the early stages of SARS-CoV-2 vaccine development, the complete vaccine platform has not been decided on by all developers, but as of April 17, 2020, approximately six are DNA and approximately 12 are RNA vaccines [2,3].

DNA Vaccines

With the DNA vaccines, developers are testing different entry mechanisms: needle injection plus electroporation (Takis, Karolinska Institute and Inovio Pharmaceuticals) and needle-free systems (Osaka University and Immunomic Therapeutic) [2,6,7]. The vaccines administered by the two different needle-free platforms (ActranzaTM  lab and PharmaJet Tropis Needle-Free Injector System) and the Inovio Pharmaceutical candidate will be injected intradermally [8], and the Takis and Karolinska Institute DNA vaccine candidates will be administered by the intramuscular route [6].

Most DNA vaccine developers have not revealed which genes they are administering in the vaccine, but Zydus Cadila has stated they are using membrane protein [2]. Of the SARS-CoV-2 DNA vaccines, the Immunomic Therapeutics candidate is the most unique; gene sequences will be chosen on the basis of their predicted ability to stimulate a strong immune response (selected for in collaboration with EpiVax) and will be ligated to the lysosomal-associated membrane protein gene [9].

RNA Vaccines

The design of the RNA vaccines is more uncertain. Most of the delivery platforms have been stated or are likely to be lipid nanoparticles (LNPs) [2]. However, BioNTech has three different lipid delivery platforms (lipoplexes, LNPs and polyplexes) [10] and has not stated which one they are using. The delivery platform that Arcturus Therapeutics will use, the LUNAR system of Synthetic Genomics, is supposed to be widely applicable for multiple inoculation routes and target tissues [11]. However, few developers have stated their inoculation route or the tissue they are targeting their LNPs to [12]. Two developers (Arcturus Therapeutics, Imperial College London) are using self-replicating mRNA [2,12], two (Translate Bio, Curevac) are using unmodified optimized mRNA sequences [13,14], and one (BioNTech) is currently still testing its three different RNA formats [15]. Many companies are likely to use the major structural protein (spike) as the gene of choice, but not all developers have explicitly said so [12].

Despite this early stage of development, one RNA vaccine (mRNA-1273, made through a National Institute of Allergy and Infectious Diseases and Moderna partnership) and one DNA vaccine (INO-4800, made by Inovio Pharmaceuticals) are already in phase 1 clinical trials, attesting to the greater speed of nucleic acid vaccine development. Both of these developers have previous experience working on coronavirus vaccines [16,17].

There is still a long road ahead for these vaccine developers, but I’m betting one of these nucleic acid­–based vaccines will win the SARS-CoV-2 vaccine race.

Are you involved in COVID-19 vaccine development? To empower your further exploration, Elsevier has launched the Coronavirus Research Hub, aimed to provide you, as an individual researcher, free access to a selection of Elsevier content and services through 28th October 2020. Visit the Research Hub and join your fellow researchers to bring this crisis to an end.


1. World Health Organization. Coronavirus (COVID19) map. Accessed April 16, 2020.

2. World Health Organization. Draft landscape of COVID-19 candidate vaccines -11 April 2020. Accessed April 14, 2020.

3. Craven J. COVID-19 vaccine tracker. Accessed April 15, 2020.

4. Rauch S, Jasny E, Schmidt KE, Petsch B.  New vaccine technologies to combat outbreak situations. Front Immunol 2018;9:1963. doi: 10.3389/fimmu.2018.01963.

5. Pronker ES, Weenen TC, Commandeur H, Claassen EH, Osterhaus AD. Risk in vaccine research and development quantified. PLoS One. 2013;8(3):e57755. doi: 10.1371/journal.pone.0057755.

6. Takis. DNA Electro Gene Transfer. Accessed April 17, 2020.

7. DAICEL Corporation. March 13, 2020 press release. Accessed April 17, 2020.

8. Safety, tolerability and immunogenicity of INO-4800 for COVID-19 in healthy volunteers. NCT04336410.

9. Immunomic Therapeutics. ITI forms collaboration with EpiVax & PharmaJet to develop novel vaccine candidate against COVID-19 using its investigational UNITE platform. Press release April 9, 2020.

10. BioNTech. mRNA therapeutics. Accessed April 17, 2020.

11. Arcturus Therapeutics. Technologies. Accessed April 17, 2020.

12. Arcturus Therapeutics. Arcturus Therapeutics announces clinical trial timeline for its COVID-19 vaccine. Posted April 9, 2020. Accessed April 17, 2020.

13. Translate Bio. Scientific platform. Accessed April 17, 2020.

14. Armbruster N, Jasny E, Petsch B. Advances in RNA vaccines for preventive indications: a case study of a vaccine against rabies. Vaccines (Basel). 2019;7(4). pii: E132. doi: 10.3390/vaccines7040132.

15. BioNTech. Infectious disease immunotherapies. Accessed April 17, 2020.

16. Phase I, open label dose ranging safety study of GLS-5300 in healthy volunteers. NCT02670187.

17. Phase I study of a vaccine for severe acute respiratory syndrome (SARS). NCT00099463.

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