The Early Discoveries of RNA and DNA Vaccination

Dr. Malone is the inventor of mRNA vaccines (and DNA vaccines). He also discovered lipid mediated and naked RNA transfection technologies.

It all started when he was at the Salk Institute in 1987 and 1988. There, he pioneered in-vitro RNA transfection and also in-vivo RNA transfection (in frog embryos, as well as mice).

This resulted in his seminal paper: Cationic liposome-mediated RNA transfection RW Malone, PL Felgner, IM Verma. Proceedings of the National Academy of Sciences (PNAS) 86 (16), 6077-6081

His filed patent and disclosures from the Salk included in-vivo RNA transfection and also methods for mRNA stabilization - now being claimed as invented by others. These are available for review.

His research was continued at Vical in 1989, where the first in-vivo mammalian rat experiments were designed by him. The mRNA, constructs, reagents were developed at the Salk institute and at Vical by Dr. Malone, this included dosing amounts for the in-vivo experiments. RNA and DNA were sent to Dr. Jon Wolff via Fedex. Dr.Wolff at the University of Wisconsin injected mice and rats. The initial patent disclosures for RNA and DNA vaccination were written by Dr. Malone in 1988-1989. Dr. Malone was also an inventor of DNA vaccines in 1988 and 1989.

This body of work resulted in over 10 patents and numerous publications, yielding about 7000 citations for this work. The paper was the first showing data for DNA and RNA side by side for in-vivo (the first paper for in-vivo DNA):

Direct gene transfer into mouse muscle in vivo. Wolff JA, Malone RW, et al. Science. 1990;247(4949 Pt 1):1465-8. Cited in 4,750 articles, is the result of that work.

In 1989, research was performed that gave rise to the 10+ groundbreaking patents on mRNA vaccination, all with a priority date of March 3, 1989. This is the same priority date as the Salk Patent application, showing that the two institutions were working together (without Robert’s knowledge). These patents are the first published research on mRNA vaccination. The titles and links to the patents are listed in the documents below. These patents have proof of principle experiments on mRNA vaccines - that clearly document that the invention worked and that these are the first experiments showing this.

Vical was to license the Salk Technology. Instead, they hired Robert’s thesis advisor from the Salk and soon after, the Salk dropped the patent and Vical never pursued a license from the Salk. Due to an employee contract with Vical, this stopped Robert from working in the field commercially for a decade. Vical claimed all the Salk research happened at Vical and sent a cease and desist letter.

Dr. Malone carried on his research into mRNA vaccination during the 1990s, culminating in a mucosal patent that was issued in 2000. He also helped revolutionized the field of cationic liposomes for the use in RNA vaccinations. This work was so far ahead of its time, that only now is the world turning to mucosal mRNA vaccination as a method of immunization. For a listing of some of his work, see the publications at the end of this page.

Scientifically trained at UC Davis, UC San Diego, and at the Salk Institute Molecular Biology and Virology laboratories, Dr. Malone received his medical training at Northwestern University (MD) and Harvard University Medical School (Clinical Research Post Graduate) , and in Pathology at UC Davis, He has almost 100 peer-reviewed publications, and has been an invited speaker at about 50 conferences.