Modifications in Therapeutic Oligonucleotides Improving the Delivery

Dovydenko, Ilya; Venyaminova, Alya G.; Pyshnyi, D. V.; Tarassov, Ivan; Entelis, Nina

doi:10.1007/978-3-319-34175-0_14

Cited by 2 publications

(1 citation statement)

References 78 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Modified oligonucleotides are widely used as a convenient instrument in numerous scientific fields including medicine [1][2][3]. While being applied as therapeutics, oligonucleotides contain chemical modifications in their structure that enhance several crucial properties [4][5][6]. One of them is the oligonucleotide cellular uptake and its further intracellular accumulation.…”

Section: Introductionmentioning

confidence: 99%

Fork- and Comb-like Lipophilic Structures: Different Chemical Approaches to the Synthesis of Oligonucleotides with Multiple Dodecyl Residues

Zharkov,

Mironova,

Markov

et al. 2023

IJMS

View full text Add to dashboard Cite

Lipophilic oligonucleotide conjugates represent a powerful tool for nucleic acid cellular delivery, and many methods for their synthesis have been developed over the past few decades. In the present study, a number of chemical approaches for the synthesis of different fork- and comb-like dodecyl-containing oligonucleotide structures were performed, including use of non-nucleotide units and different types of phosphate modifications such as alkyl phosphoramidate, phosphoryl guanidine, and triazinyl phosphoramidate. The influence of the number of introduced lipophilic residues, their mutual arrangement, and the type of formed modification backbone on cell penetration was evaluated. The results obtained indicate great potential in the developed chemical approaches, not only for the synthesis of complex oligonucleotide structures but also for the fine-tuning of their properties.

show abstract

Section: Introductionmentioning

confidence: 99%

Fork- and Comb-like Lipophilic Structures: Different Chemical Approaches to the Synthesis of Oligonucleotides with Multiple Dodecyl Residues

Zharkov,

Mironova,

Markov

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

Lipophilic Conjugates for Carrier-Free Delivery of RNA Importable into Human Mitochondria

Dovydenko

Meschaninova

Heckel

et al. 2021

Methods in Molecular Biology

Self Cite

View full text Add to dashboard Cite

Defects in human mitochondrial genome can cause a wide range of clinical disorders which still do not have efficient therapies. The natural pathway of small non-coding RNA import can be exploited to address into mitochondria therapeutic RNAs. To create an approach of carrier-free targeting of RNA into living human cells, we designed conjugates containing a cholesterol residue and developed the protocols of chemical synthesis of oligoribonucleotides conjugated with cholesterol residue through cleavable pH-triggered hydrazone bond. The biodegradable conjugates of importable RNA with cholesterol can be internalized by cells in a carrier-free manner; RNA can then be released in the late endosomes due to a change in pH and partially targeted into mitochondria. Here we provide detailed protocols for solid-phase and "in solution" chemical synthesis of oligoribonucleotides conjugated to a cholesterol residue through a hydrazone bond. We describe the optimization of the carrier-free cell transfection with these conjugated RNA molecules and methods for evaluating the cellular and mitochondrial uptake of lipophilic conjugates.

show abstract

Modifications in Therapeutic Oligonucleotides Improving the Delivery

Cited by 2 publications

References 78 publications

Fork- and Comb-like Lipophilic Structures: Different Chemical Approaches to the Synthesis of Oligonucleotides with Multiple Dodecyl Residues

Fork- and Comb-like Lipophilic Structures: Different Chemical Approaches to the Synthesis of Oligonucleotides with Multiple Dodecyl Residues

Lipophilic Conjugates for Carrier-Free Delivery of RNA Importable into Human Mitochondria

Contact Info

Product

Resources

About