Throughout my career I have advocated rigorous evaluations to inform judgement about the benefits/risks of new medicines and I have been gratified by the progression in the science of clinical evaluations. The most effective science begins with a clearly defined hypothesis that is fully justified by prior data, then a well-designed experiment with all the necessary controls. Once an experiment is complete, a scientist’s job … Continue reading The Problem with Statistical Significance »

One of the long-term goals of my laboratory has been to understand the cellular factors that influence the activities of antisense oligonucleotides (ASOs). For example, we have used a well-defined and structurally characterized model system, the SOD1 mini-gene, to evaluate the effects of RNA structure, RNA binding proteins, repetitive sequences, the strength of splicing signals, the length and position of introns and other factors on … Continue reading Understanding the Molecular Mechanisms of ASOs; Translation Effects on ASO Activity »

One of the most frequently asked questions about antisense oligonucleotides (ASOs) is, “How do ASOs enter cells?” In the past few years, my research group has provided ever more detailed answers to that question and have also set out to answer an equally important question: “Where do ASOs go once inside cells and how do they get there?” In a review published in Nature Biotechnology, … Continue reading Cellular Uptake and Trafficking of ASOs »

One of my interests is to understand the fine details of the molecular mechanisms for which antisense oligonucleotides (ASOs) may be designed. Today, we have a very high-level understanding of many of the molecular mechanisms and have successfully expanded the repertoire of well-understood mechanisms of action. This knowledge enables the design of better performing RNA-targeted medicines and expands the therapeutic potential of antisense technology. In … Continue reading Understanding the Molecular Mechanisms of ASOs »

RNA-targeted drug discovery and development is beginning to deliver important and broad therapeutic benefits. The field also continues to progress at a rapid pace with advances in the technology being converted into enhanced performance of new medicines in the clinic. The advances are so broad and occurring so fast that it is difficult even for experts in the field to stay abreast of the progress. … Continue reading Progress and Future Opportunities for RNA-targeted Therapeutics »

Two properties of antisense technology that have proven to be a bit difficult for observers to fully understand are first, that within a given chemical class of antisense oligonucleotides (ASOs), the behavior of individual ASOs is reasonably consistent. This derives from the fact that within a given chemical class, physico-chemical properties are quite similar as the ASOs differ only in the nucleotide sequence selected to … Continue reading New Chemical Class of Antisense Drugs Shows Promise as Transformative ASO Technology Continues to Advance »