Linear DNA based coronavirus vaccines are being developed by Takis and LineaRx (a wholly owned subsidiary of Applied DNA sciences) for the prevention of COVID-2019 infections. The linear DNA vaccine candidates will be delivered via Takis' proprietary in vivo electro-gene-transfer technology. LineaRx will use its PCR methods for the production of linear DNA which is cleaner, faster and more easily modified in comparison with DNA produced using standard methods. Preclinical study is underway in the US and Italy.
Under this programme, five DNA vaccine candidates will be developed for preclinical animal testing. Takis will use the scaled-up LinearDNA™ synthetic genes produced by Applied DNA for each of the four putative vaccines to inoculate mice, whose sera will be tested for the presence of antibodies that bind to the purified spike proteins. The positive candidates that bind to spike will be tested for their ability to neutralize COVID-19 by preventing uptake of the virus in cells in culture and in animal models  .
In March 2020, LineaRx (subsidiary of Applied DNA Sciences) expanded its joint development agreement with Takis for COVID-19 vaccine development program to include a fifth vaccine candidate. Under the terms of the companies’ amended Joint Development Agreement, Takis will use the scaled-up LinearDNA synthetic genes produced by Applied DNA for each of the five putative vaccines to inoculate mice whose sera will be tested for the presence of antibodies that bind to the purified Spike proteins. Those positive candidates that bind to Spike will be tested for their ability to neutralize COVID-19 by preventing uptake of the virus in cells in culture and in animal models. Previously in February 2020, LineaRx expanded its joint development agreement with Takis for the preclinical development of a linear DNA vaccine against COVID-2019 infections. Earlier in September 2018, LineaRx entered into a joint development agreement with Takis for the discovery and development of DNA based anti-cancer vaccines. Under the terms of the agreement, both companies will jointly develop linear DNA expression vectors for two of Takis anticancer vaccine candidates using LineaRx's linear DNA technology. Linear DNA amplicons carrying the DNA sequences for Takis vaccine candidates will be delivered to preclinical animal models via Takis's proprietary electroporation technology for measurement of the antigen-specific immune responses. Further details of the agreement were not disclosed.   
Key Development Milestones
In May 2020, Applied DNA sciences and Takis Biotech announced that nutralising antibodies have been produced in test animals after the first injections of the DNA vaccine candidates against the Spike protein (product of the S gene) of the SARS-CoV-2 virus that causes COVID-2019 infections  .
In April 2020, LineaRx announced that it has completed qualification, production and shipment of five vaccine candidates to Takis Biotech in Italy. In March 2020, LineaRx and Takis Biotech had announced expansion of their COVID-2019 vaccine development program to include a fifth vaccine candidate. Along with the planned Takis animal trials, LineaRx plans to prepare for cGMP production of selected vaccine candidate(s) to support human trials scheduled to begin in fall   .
In March 2020, Italian Ministry of Health approved to test the linear DNA based coronavirus vaccines in animal models. The preliminary examination to test the tolerability and efficacy will be conducted at the Spallanzani Institute  .
Early research of linear DNA vaccines against COVID-2019 infections is ongoing  .