Delivery of oligonucleotide‐based therapeutics: challenges and opportunities
Abstract Nucleic acid‐based therapeutics that regulate gene expression have been developed towards clinical use at a steady pace for several decades, but in recent years the field has been accelerating. To date, there are 11 marketed products based on antisense oligonucleotides, aptamers and small i...
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Springer Nature
2021-04-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202013243 |
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| author | Suzan M Hammond Annemieke Aartsma‐Rus Sandra Alves Sven E Borgos Ronald A M Buijsen Rob W J Collin Giuseppina Covello Michela A Denti Lourdes R Desviat Lucía Echevarría Camilla Foged Gisela Gaina Alejandro Garanto Aurelie T Goyenvalle Magdalena Guzowska Irina Holodnuka David R Jones Sabine Krause Taavi Lehto Marisol Montolio Willeke Van Roon‐Mom Virginia Arechavala‐Gomeza |
| author_facet | Suzan M Hammond Annemieke Aartsma‐Rus Sandra Alves Sven E Borgos Ronald A M Buijsen Rob W J Collin Giuseppina Covello Michela A Denti Lourdes R Desviat Lucía Echevarría Camilla Foged Gisela Gaina Alejandro Garanto Aurelie T Goyenvalle Magdalena Guzowska Irina Holodnuka David R Jones Sabine Krause Taavi Lehto Marisol Montolio Willeke Van Roon‐Mom Virginia Arechavala‐Gomeza |
| author_sort | Suzan M Hammond |
| collection | DOAJ |
| description | Abstract Nucleic acid‐based therapeutics that regulate gene expression have been developed towards clinical use at a steady pace for several decades, but in recent years the field has been accelerating. To date, there are 11 marketed products based on antisense oligonucleotides, aptamers and small interfering RNAs, and many others are in the pipeline for both academia and industry. A major technology trigger for this development has been progress in oligonucleotide chemistry to improve the drug properties and reduce cost of goods, but the main hurdle for the application to a wider range of disorders is delivery to target tissues. The adoption of delivery technologies, such as conjugates or nanoparticles, has been a game changer for many therapeutic indications, but many others are still awaiting their eureka moment. Here, we cover the variety of methods developed to deliver nucleic acid‐based therapeutics across biological barriers and the model systems used to test them. We discuss important safety considerations and regulatory requirements for synthetic oligonucleotide chemistries and the hurdles for translating laboratory breakthroughs to the clinic. Recent advances in the delivery of nucleic acid‐based therapeutics and in the development of model systems, as well as safety considerations and regulatory requirements for synthetic oligonucleotide chemistries are discussed in this review on oligonucleotide‐based therapeutics. |
| format | Article |
| id | doaj-art-76e52486fd764de6bb07b4e5106b079a |
| institution | DOAJ |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2021-04-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-76e52486fd764de6bb07b4e5106b079a2025-08-20T03:06:00ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842021-04-0113412310.15252/emmm.202013243Delivery of oligonucleotide‐based therapeutics: challenges and opportunitiesSuzan M Hammond0Annemieke Aartsma‐Rus1Sandra Alves2Sven E Borgos3Ronald A M Buijsen4Rob W J Collin5Giuseppina Covello6Michela A Denti7Lourdes R Desviat8Lucía Echevarría9Camilla Foged10Gisela Gaina11Alejandro Garanto12Aurelie T Goyenvalle13Magdalena Guzowska14Irina Holodnuka15David R Jones16Sabine Krause17Taavi Lehto18Marisol Montolio19Willeke Van Roon‐Mom20Virginia Arechavala‐Gomeza21Department of Paediatrics, University of OxfordDepartment of Human Genetics, Leiden University Medical CenterDepartment of Human Genetics, Research and Development Unit, National Health Institute Doutor Ricardo JorgeDepartment of Biotechnology and Nanomedicine, SINTEF ASDepartment of Human Genetics, Leiden University Medical CenterDepartment of Human Genetics and Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical CenterDepartment of Biology, University of PadovaDepartment of Cellular, Computational and Integrative Biology ‐ CIBIO, University of TrentoCentro de Biología Molecular Severo Ochoa UAM‐CSIC, CIBERER, IdiPaz, Universidad Autónoma de MadridSQY TherapeuticsDepartment of Pharmacy, Faculty of Health and Medical Sciences, University of CopenhagenVictor Babes National Institute of PathologyDepartment of Human Genetics and Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical CenterUniversité Paris‐Saclay, UVSQ, Inserm, END‐ICAPDepartment of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences – SGGWInstitute of Microbiology and Virology, Riga Stradins UniversityMHRA 10 South ColonnadeDepartment of Neurology, Friedrich‐Baur‐Institute, Ludwig‐Maximilians‐University of MunichInstitute of Technology, University of TartuDuchenne Parent Project EspañaDepartment of Human Genetics, Leiden University Medical CenterNeuromuscular Disorders Group, Biocruces Bizkaia Health Research InstituteAbstract Nucleic acid‐based therapeutics that regulate gene expression have been developed towards clinical use at a steady pace for several decades, but in recent years the field has been accelerating. To date, there are 11 marketed products based on antisense oligonucleotides, aptamers and small interfering RNAs, and many others are in the pipeline for both academia and industry. A major technology trigger for this development has been progress in oligonucleotide chemistry to improve the drug properties and reduce cost of goods, but the main hurdle for the application to a wider range of disorders is delivery to target tissues. The adoption of delivery technologies, such as conjugates or nanoparticles, has been a game changer for many therapeutic indications, but many others are still awaiting their eureka moment. Here, we cover the variety of methods developed to deliver nucleic acid‐based therapeutics across biological barriers and the model systems used to test them. We discuss important safety considerations and regulatory requirements for synthetic oligonucleotide chemistries and the hurdles for translating laboratory breakthroughs to the clinic. Recent advances in the delivery of nucleic acid‐based therapeutics and in the development of model systems, as well as safety considerations and regulatory requirements for synthetic oligonucleotide chemistries are discussed in this review on oligonucleotide‐based therapeutics.https://doi.org/10.15252/emmm.202013243deliveryoligonucleotidespreclinical modelsRNA therapeuticssafety |
| spellingShingle | Suzan M Hammond Annemieke Aartsma‐Rus Sandra Alves Sven E Borgos Ronald A M Buijsen Rob W J Collin Giuseppina Covello Michela A Denti Lourdes R Desviat Lucía Echevarría Camilla Foged Gisela Gaina Alejandro Garanto Aurelie T Goyenvalle Magdalena Guzowska Irina Holodnuka David R Jones Sabine Krause Taavi Lehto Marisol Montolio Willeke Van Roon‐Mom Virginia Arechavala‐Gomeza Delivery of oligonucleotide‐based therapeutics: challenges and opportunities EMBO Molecular Medicine delivery oligonucleotides preclinical models RNA therapeutics safety |
| title | Delivery of oligonucleotide‐based therapeutics: challenges and opportunities |
| title_full | Delivery of oligonucleotide‐based therapeutics: challenges and opportunities |
| title_fullStr | Delivery of oligonucleotide‐based therapeutics: challenges and opportunities |
| title_full_unstemmed | Delivery of oligonucleotide‐based therapeutics: challenges and opportunities |
| title_short | Delivery of oligonucleotide‐based therapeutics: challenges and opportunities |
| title_sort | delivery of oligonucleotide based therapeutics challenges and opportunities |
| topic | delivery oligonucleotides preclinical models RNA therapeutics safety |
| url | https://doi.org/10.15252/emmm.202013243 |
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