Category Archives: Blogs

Blogs

The n-Lorem Foundation: up and running and making a difference in the lives of rare disease patients

Patients and families with genetic diseases that afflict one or very few patients in the world pose unique challenges to the healthcare industry. It is gratifying that the National Institutes of Health (NIH) and other institutions in the U.S. have begun to address identifying such patients and harnessing the power of modern genomics to diagnose and identify the molecular causes of these diseases. In fact, … Continue reading The n-Lorem Foundation: up and running and making a difference in the lives of rare disease patients »

Blogs

Mechanisms that improve therapeutic index

Mechanisms of ASO toxicities and the structure activity relationships that improve therapeutic index Last year, we published a landmark paper that described a general mechanism that explains how toxic ASOs produce toxicities and provided a straightforward medicinal chemistry solution to enhance safety with little effect on potency (Shen et.al., 2019). We have now published several papers that extend our observations and broaden the understanding of … Continue reading Mechanisms that improve therapeutic index »

Blogs

NEJM highlights Waylivra™ (volanesorsen)

The results of the Phase three study of WAYLIVRA (volanesorsen) in patients with familial chylomicronemia syndrome (FCS) were recently published in the New England Journal of Medicine (NEJM) (Witzum, et al., 2019). FCS patients have severely elevated triglycerides (often >2000 mg/dl). This drug is now approved in the EU and being considered for approval by the U.S. Food and Drug Administration (FDA). To date, it … Continue reading NEJM highlights Waylivra™ (volanesorsen) »

Blogs

Solving a decades’ old scientific mystery brings us closer to discovering the perfect drug

Recently, my group and I published an important paper in Nature Biotechnology. It is important because it provides an answer to a question that has vexed scientists working in antisense oligonucleotide (ASO) technology for more than 20 years: “Why are some ASOs toxic?” In this paper for the first time we provide a step-by-step molecular mechanism that answers this question. Even more excitingly, we show … Continue reading Solving a decades’ old scientific mystery brings us closer to discovering the perfect drug »

Blogs

The Problem with Statistical Significance

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 »

Blogs

Understanding the Molecular Mechanisms of ASOs; Translation Effects on ASO Activity

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 »

Blogs

Cellular Uptake and Trafficking of ASOs

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 »

Blogs

Understanding the Molecular Mechanisms 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 »

Blogs

Progress and Future Opportunities for RNA-targeted Therapeutics

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 »