RNA technologies make targeted immune activation possible

MEDICA 2022 is right around the corner, ready to deliver insights into the advancements and innovations in laboratory medicine. One of the key topics of the MEDICA LABMED Forum is RNA technologies and the wide range of applications that involve cell biology. RNA technologies not only enable Covid-19 vaccines but promise an array of treatment options for genetic diseases, in and beyond oncology.

In this MEDICA-tradefair.com interview, Dr. Peter Quick illustrates how new modalities in RNA technologies are affecting laboratory medicine.

Dr. Quick, what role do RNA technologies play in laboratory medicine?

Dr. Peter Quick: Cell biology is becoming more and more precise whilst genetic engineering is getting ever easier to control. We have entered the era of nucleic acid therapeutics. It is about future applications of RNA technologies, moving far beyond the current vaccines, and it is about increasing networking with gene and cell therapies (CGT). Expect to see competition, mutual reinforcement, and analogies between the two fields, which will include support from laboratory medicine and other service providers, most notably as it relates to life science research technologies.

It is essential to address the following challenges in this setting: How targeted and safely are the tools delivered into the body – either via lipid- and polymer-based nanoparticles (RNA) or by viruses (CGT)? Is there an unwanted activation of immune response? Every process step also hinges on quality control with standardized and preferably automated tests. And it raises the following questions: Is therapy success predictable? And can we reduce costs?

What do new modalities in RNA technologies mean for laboratory medicine?

Quick: By the end of 2021, the FDA (Food and Drug Administration) had approved about a dozen RNA therapies, the majority of which are based on antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) candidates for genetic diseases. But today’s development moves past genetic diseases and includes RNA vaccines and therapeutic agents used in oncology, ophthalmology, infectious and metabolic diseases, and entails clinical trials of more than two dozen novel procedures in 2022. Special attention is paid to non-coding RNA due to its tumor specificity. Another group of RNA molecules, transfer RNAs (abbreviated tRNA), may play a part in regulating ribosomal biogenesis, which is important when it comes to malignant conditions, meaning wherever there is an overgrowth of cells as is the case in oncology or autoimmune diseases.

Yet the biggest obstacle with RNA therapeutics still pertains to simplifying delivery while getting past the first-pass effect of the liver. That’s because when a drug is converted during its first passage through the liver, the subsequent biochemical conversion can result in an active or inactive metabolite. Original siRNA LNP (liquid nanoparticle) formulations outlined the pathway for Covid-19 mRNA vaccines. It’s very beneficial if you can produce these nanoparticles with repetitious accuracy and load them with long RNA sequences. However, LNPs can promote a strong immune response, which is a benefit when it comes to vaccines but rather unwelcome in case of Huntington's disease or SMA (spinal muscular atrophy). These challenges are being addressed by several novel approaches typically not yet known to the medical audience.

Which RNA technologies currently hold the greatest promise to drive development?

Quick: This will require quality control, diagnostics, and therapeutic support of extraordinarily high quality. From my perspective, sequencing methods, assays for delivery systems qualification, flow cytometry, and functional bioassays show great potential.

What is your current research focus in RNA technologies?

Quick: As Spokesperson of the Board of the Life Science Research Department of the Association of the Diagnostics Industry (VDGH), which has been supporting the MEDICA LABMED Forum for years, I speak for all LSR member companies that are working to advance these technologies. I also represent the member company Promega GmbH, which I started building in 1996. Within this context, Promega focuses on functional bioassays and on STR analysis, which is known as a mainstay of forensics.

What do you expect from the lectures on RNA technologies at the MEDICA LABMED FORUM?

Quick: These lectures impart basic knowledge, discuss the latest progress, and point out exciting opportunities. They essentially “whet your appetite” for a deeper understanding and appreciation of the subject. They also create excitement over the duality shown to the previous paths of gene and cell therapy, which will be addressed by subsequent lectures.

Why do you think MEDICA is the right platform to address this topic?

Quick: The trade fair showcases solutions and products that are available or will be available shortly. There is a need for guidance and for building a pathway to the future as industry and academia are eager to understand and learn everything about the trends - and are ready to connect and seize opportunities together. That’s why on Thursday, November 17th, we get the chance to meet speakers from both industry and basic research at the MEDICA LABMED FORUM.