The magic bullet: a tribute to Fritz Eckstein

The first encounter I ever had with Fritz Eckstein was in 1969 at Stanford University to discuss a polyribonucleotide in which the phosphate was replaced by thiophosphate groups, engendering increased interferon induction (i.e. antiviral activity). His research work then focused on the versatility of oligonucleotides as potential therapeutics. Spanning a period of several decades, various other leads of research were undertaken, i.e. 2'- and 3'-amino or -azido-substituted deoxyribonucleoside analogs, hammerhead ribozymes, small non-coding mRNAs (siRNAs, miRNAs) for monitoring gene therapy, and thiophosphate-substituted nucleotide analogs to be used in RNA and DNA sequencing. This exemplary scientific career generated not one but a multitude of magic bullets for biomedical research and application.