Maggie's Farm

In 1989, Robert W. Malone, P. Felgner, et. al. developed a high-efficiency in-vitro and in-vivo RNA transfection system using cationic liposomes, which were used "to directly introduce RNA into whole tissues and embryos", as well as various cells types. The term and idea of "RNA as a drug" is first described in this paper. [15] Then, in 1990, Jon A. Wolff, Robert W Malone, et. al. demonstrated the idea of nucleic acid-encoded drugs by direct injecting in vitro transcribed (IVT) mRNA or plasmid DNA (pDNA) into the skeletal muscle of mice which expressed the encoded protein in the injected muscle. These studies were the first evidence that in vitro transcribed (IVT) mRNA could deliver the genetic information to produce proteins within living cell tissue. [16][17]

The first mRNA vaccine experiments were carried out by P. Felgner, J. Wolff, G. Rhodes, R.W. Malone and D. Carson. P. They completed a number of mRNA vaccination studies that resulted in nine patents on mRNA vaccination with a shared priority date of March 21, 1989. One experiment documented that NEF (an HIV protein) mRNA vaccination in mice, followed by HIV challenge reduced positively stained cells by 2-fold and p24 expression was reduced by 50% at eight weeks. [18][19][20]

In 1993, Martinon demonstrated that liposome-encapsulated RNA could stimulate T-cells in vivo, and in 1994, Zhou & Berglund published the first evidence that RNA could be used as a vaccine to elicit both humoral and cellular immune response against a pathogen.[21][22]

Hungarian biochemist Katalin Karikó attempted to solve some of the main technical barriers to introducing mRNA into cells in the 1990s. Karikó partnered with American immunologist Drew Weissman, and by 2005 they published a joint paper that solved one of the key technical barriers by using modified nucleosides to get mRNA inside cells without setting off the body's defense system.[23] Harvard stem cell biologist Derrick Rossi (then at Stanford) read Karikó and Weissman's paper and recognized that their work was "groundbreaking",[23] and in 2010 founded the mRNA-focused biotech Moderna along with Robert Langer, who also saw its potential in vaccine development.[23] In 2013, DARPA, the US government organization responsible for emerging technologies for use by the military, saw the potential of the technology for defense against pandemics and invested $25 million in the company.[24] Like Moderna, BioNTech also licensed Karikó and Weissman's work.[23]