Analytical techniques currently used in the pharmaceutical industry for the quality control of RNA-based therapeutics and ongoing developments

Demelenne, Alice; Servais, Anne-Catherine; Crommen, Jacques; Fillet, Marianne

doi:10.1016/j.chroma.2021.462283

Cited by 13 publications

(14 citation statements)

References 111 publications

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“…They constitute an integral part of the mandatory quality control as well as the isolation of high purity intermediates required for products whose synthesis is performed serially. It must be highlighted that in mRNA production, utmost purity of the final product is not only a safety issue, but also a matter of therapeutical efficacy and shelf-life longevity, since contaminants can compromise both shelf-life of the finalized product as well as illicit unwanted immune responses [ 85 , 86 , 87 ]…”

Section: Analytical Approachesmentioning

confidence: 99%

mRNA Therapeutic Modalities Design, Formulation and Manufacturing under Pharma 4.0 Principles

et al. 2021

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In the quest for a formidable weapon against the SARS-CoV-2 pandemic, mRNA therapeutics have stolen the spotlight. mRNA vaccines are a prime example of the benefits of mRNA approaches towards a broad array of clinical entities and druggable targets. Amongst these benefits is the rapid cycle “from design to production” of an mRNA product compared to their peptide counterparts, the mutability of the production line should another target be chosen, the side-stepping of safety issues posed by DNA therapeutics being permanently integrated into the transfected cell’s genome and the controlled precision over the translated peptides. Furthermore, mRNA applications are versatile: apart from vaccines it can be used as a replacement therapy, even to create chimeric antigen receptor T-cells or reprogram somatic cells. Still, the sudden global demand for mRNA has highlighted the shortcomings in its industrial production as well as its formulation, efficacy and applicability. Continuous, smart mRNA manufacturing 4.0 technologies have been recently proposed to address such challenges. In this work, we examine the lab and upscaled production of mRNA therapeutics, the mRNA modifications proposed that increase its efficacy and lower its immunogenicity, the vectors available for delivery and the stability considerations concerning long-term storage.

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Section: Analytical Approachesmentioning

confidence: 99%

mRNA Therapeutic Modalities Design, Formulation and Manufacturing under Pharma 4.0 Principles

et al. 2021

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“…Oligonucleotide therapeutics have a broad spectrum of indications and comprise a rapidly expanding category of drugs that may change the standard of care for many diseases 1–4. One of the big challenges that therapeutic oligonucleotides face is their instability, since they are highly susceptible to degradation by nucleases in vivo.…”

Section: Introductionmentioning

confidence: 99%

“…Oligonucleotide therapeutics have a broad spectrum of indications and comprise a rapidly expanding category of drugs that may change the standard of care for many diseases. 1 , 2 , 3 , 4 One of the big challenges that therapeutic oligonucleotides face is their instability, since they are highly susceptible to degradation by nucleases in vivo. Various chemical modifications on the base, sugar, or phosphate backbone of synthetic oligonucleotides have been developed to improve their stability to nuclease digestion as well as efficacy and safety.…”

Section: Introductionmentioning

confidence: 99%

Tandem mass spectrometric sequence characterization of synthetic thymidine‐rich oligonucleotides

et al. 2022

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“…Analytical quality controls of the RNA molecule are therefore critical to allow the identification of alterations to the molecule and allow mitigation and prevention strategies to be put into place. A variety of analytical methods have been used to characterise the RNA drug substance in process including visual appearance, subvisible particles, UV and fluorescence spectroscopy, agarose gel electrophoresis, capillary electrophoresis (CE), chromatography (SEC – size-exchange chromatography, reverse-phase chromatography (RP), anion-exchange chromatography (AEX)), light scattering (dynamic light scattering – DLS, SLS – static light scattering, MALS – multi-angle light scattering), circular dichroism (CD), reverse transcriptase PCR (RT-PCR) and liquid chromatography - mass spectrometry (LS-MS) (15, 16).…”

Section: Introductionmentioning

confidence: 99%

Biophysical characterisation of the structure of a SARS-CoV-2 self-amplifying - RNA (saRNA) vaccine

Myatt

Wharram

Graham

et al. 2022

Preprint

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The current SARS-Covid-2 pandemic has led to an acceleration of messenger ribonucleic acid (mRNA) vaccine technology. The development of production processes for these large mRNA molecules, especially self-amplifying mRNA (saRNA) has required concomitant development of analytical characterisation techniques. Characterising the purity, shape and structure of these biomolecules is key to their successful performance as drug products. This paper describes the biophysical characterisation of the Imperial College London Self amplifying viral RNA vaccine (IMP 1) developed for SARS CoV 2. A variety of analytical techniques have been used to characterise the IMP 1 RNA molecule. In this paper we use UV spectroscopy, dynamic light scattering (DLS), size exclusion chromatography small angle scattering (SEC-SAXS) and circular dichroism (CD) to determine key biophysical attributes of IMP-1. Each technique provides important information about the concentration, size, shape, structure and purity of the molecule.

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Analytical techniques currently used in the pharmaceutical industry for the quality control of RNA-based therapeutics and ongoing developments

Cited by 13 publications

References 111 publications

mRNA Therapeutic Modalities Design, Formulation and Manufacturing under Pharma 4.0 Principles

mRNA Therapeutic Modalities Design, Formulation and Manufacturing under Pharma 4.0 Principles

Tandem mass spectrometric sequence characterization of synthetic thymidine‐rich oligonucleotides

Biophysical characterisation of the structure of a SARS-CoV-2 self-amplifying - RNA (saRNA) vaccine

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