Nucleic acid therapeutics, 2018-06, Vol.28 (3), p.178
2018
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Details
- Autor(en) / Beteiligte
- Titel
- Current Challenges in Delivery and Cytosolic Translocation of Therapeutic RNAs
- Ist Teil von
- Nucleic acid therapeutics, 2018-06, Vol.28 (3), p.178
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2018
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- RNA interference (RNAi) is a fundamental cellular process for the posttranscriptional regulation of gene expression. RNAi can exogenously be modulated by small RNA oligonucleotides, such as microRNAs (miRNAs) and small interfering RNAs (siRNAs), or by antisense oligonucleotides. These small oligonucleotides provided the scientific community with powerful and versatile tools to turn off the expression of genes of interest, and hold out the promise of new therapeutic solutions against a wide range of gene-associated pathologies. However, unmodified nucleic acids are highly instable in biological systems, and their weak interaction with plasma proteins confers an unfavorable pharmacokinetics. In this review, we first provide an overview of the most efficient chemical strategies that, over the past 30 years, have been used to significantly improve the therapeutic potential of oligonucleotides. Oligonucleotides targeting and delivery technologies are then presented, including covalent conjugates between oligonucleotides and targeting ligand, and noncovalent association with lipid or polymer nanoparticles. Finally, we specifically focus on the endosomal escape step, which represents a major stumbling block for the effective use of oligonucleotides as therapeutic agents. The need for approaches to quantitatively measure endosomal escape and cytosolic arrival of biomolecules is discussed in the context of the development of efficient oligonucleotide targeting and delivery vectors.
- Sprache
- Englisch
- Identifikatoren
- eISSN: 2159-3345DOI: 10.1089/nat.2017.0716Titel-ID: cdi_pubmed_primary_29883296
- Format
- –
- Schlagworte
- Amyloidosis - genetics, Amyloidosis - metabolism, Amyloidosis - pathology, Amyloidosis - therapy, Animals, Biological Transport, Cell-Penetrating Peptides - chemistry, Cell-Penetrating Peptides - metabolism, Cytosol - metabolism, Endosomes - metabolism, Gene Transfer Techniques, Genetic Therapy - methods, Humans, Lipids - chemistry, MicroRNAs - genetics, MicroRNAs - metabolism, Morpholinos - chemistry, Morpholinos - metabolism, Nanoparticles - chemistry, Nanoparticles - metabolism, Neoplasms - genetics, Neoplasms - metabolism, Neoplasms - pathology, Neoplasms - therapy, Oligonucleotides - chemistry, Oligonucleotides - metabolism, Oligonucleotides, Antisense - genetics, Oligonucleotides, Antisense - metabolism, Peptide Nucleic Acids - chemistry, Peptide Nucleic Acids - metabolism, Phosphorothioate Oligonucleotides - chemistry, Phosphorothioate Oligonucleotides - metabolism, RNA, Small Interfering - genetics, RNA, Small Interfering - metabolism