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]
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