Mucin-mediated nanocarrier disassembly for triggered uptake of oligonucleotides as a delivery strategy for the potential treatment of mucosal tumours

This work demonstrates gastric mucin-triggered nanocarrier disassembly for release of antisense oligonucleotides and consequent unassisted cellular entry as a novel oral delivery strategy.

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Preclinical Studies on Intestinal Administration of Antisense Oligonucleotides as a Model for Oral Delivery for Treatment of Duchenne Muscular Dystrophy

Molecular Therapy — Nucleic Acids ◽

10.1038/mtna.2014.62 ◽

2014 ◽

Vol 3 ◽

pp. e211 ◽

Cited By ~ 8

Author(s):

Maaike van Putten ◽

Courtney Young ◽

Sjoerd van den Berg ◽

Amanda Pronk ◽

Margriet Hulsker ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Antisense Oligonucleotides ◽

Oral Delivery ◽

Preclinical Studies

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Aptamer-iRNAs as Therapeutics for Cancer Treatment

Pharmaceuticals ◽

10.3390/ph11040108 ◽

2018 ◽

Vol 11 (4) ◽

pp. 108 ◽

Cited By ~ 14

Author(s):

Mario Soldevilla ◽

Daniel Meraviglia-Crivelli de Caso ◽

Ashwathi Menon ◽

Fernando Pastor

Keyword(s):

Cancer Therapy ◽

Cancer Treatment ◽

Antisense Oligonucleotides ◽

Tertiary Structure ◽

Potential Treatment ◽

High Affinity ◽

Different Types ◽

Systematic Evolution ◽

Exponential Enrichment ◽

Selection Of

Aptamers are single-stranded oligonucleotides (ssDNA or ssRNA) that bind and recognize their targets with high affinity and specificity due to their complex tertiary structure. Aptamers are selected by a method called SELEX (Systematic Evolution of Ligands by EXponential enrichment). This method has allowed the selection of aptamers to different types of molecules. Since then, many aptamers have been described for the potential treatment of several diseases including cancer. It has been described over the last few years that aptamers represent a very useful tool as therapeutics, especially for cancer therapy. Aptamers, thanks to their intrinsic oligonucleotide nature, present inherent advantages over other molecules, such as cell-based products. Owing to their higher tissue penetrability, safer profile, and targeting capacity, aptamers are likely to become a novel platform for the delivery of many different types of therapeutic cargos. Here we focus the review on interfering RNAs (iRNAs) as aptamer-based targeting delivered agents. We have gathered the most reliable information on aptamers as targeting and carrier agents for the specific delivery of siRNAs, shRNA, microRNAs, and antisense oligonucleotides (ASOs) published in the last few years in the context of cancer therapy.

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Oral Delivery of Antisense Oligonucleotides in Man

Journal of Pharmaceutical Sciences ◽

10.1002/jps.21084 ◽

2008 ◽

Vol 97 (1) ◽

pp. 225-236 ◽

Cited By ~ 71

Author(s):

Lloyd G. Tillman ◽

Richard S. Geary ◽

Gregory E. Hardee

Keyword(s):

Antisense Oligonucleotides ◽

Oral Delivery

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AAV-based gene therapies for the muscular dystrophies

Human Molecular Genetics ◽

10.1093/hmg/ddz128 ◽

2019 ◽

Vol 28 (R1) ◽

pp. R102-R107 ◽

Cited By ~ 21

Author(s):

Julie M Crudele ◽

Jeffrey S Chamberlain

Keyword(s):

Antisense Oligonucleotides ◽

Gene Editing ◽

Viral Vector ◽

Genetic Diseases ◽

Mrna Splicing ◽

Large Animal ◽

Potential Treatment ◽

Gene Therapies ◽

Dominant Disease ◽

Inflammatory Infiltrates

Abstract Muscular dystrophy (MD) is a group of progressive genetic diseases affecting the musculature that are characterized by inflammatory infiltrates, necrosis and connective tissue and fat replacement of the affected muscles. Unfortunately, treatments do not exist for the vast majority of MD patients. Adeno-associated viral vector (AAV)-based gene therapy is thus emerging as a potential treatment for many types of MD. Treatments strategies based on AAV are being adapted for replacement of mutant disease-causing genes, knockdown of dominant disease-causing genes using antisense oligonucleotides or inhibitory RNAs, delivery of gene editing tools such as clustered regularly interspaced short palindromic repeats/Cas9 and effecting alterations in pre-mRNA splicing and by manipulating expression levels of modifier genes. Translational and clinical trial work focused on these types of AAV treatments for Duchenne MD, various limb girdle MDs, myotonic dystrophy 1, facioscapulohumeral MD, dysferlinopathies and congenital MDs are discussed here, with a focus on recent studies, pre-clinical large animal work and many promising ongoing and upcoming AAV clinical trials.

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