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Intrathecal Delivery of Antisense Oligonucleotides in the Rat Central Nervous System
Published on: October 29, 2019
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RGD Conjugated Dendritic Polylysine for Cellular Delivery of Antisense Oligonucleotide
Journal of Nanoscience and Nanotechnology
|April 12, 2018
Summary
Modified dendritic polylysines (DPL) with RGD peptides enhance targeted delivery of antisense oligonucleotides to cells. This peptide conjugation facilitates receptor-mediated cellular uptake without toxicity, showing moderate delivery efficiency.
Area of Science:
- Biotechnology
- Nanotechnology
- Polymer Chemistry
Background:
- Dendritic polylysines (DPL) are branched polymers with positively charged surfaces.
- Their structure is suitable for delivering nucleic acids like antisense oligonucleotides (ASOs) or siRNA.
- Targeted delivery can improve therapeutic efficacy and reduce side effects.
Purpose of the Study:
- To conjugate RGD peptides onto dendritic polylysines (DPL).
- To evaluate the integrin receptor-mediated cellular delivery of ASOs using these modified DPLs.
- To assess the efficiency and toxicity of the RGD-DPL/ASO complexes.
Main Methods:
- Surface modification of DPL with cyclic RGD (or iRGD) peptides via conjugation.
- Monitoring conjugation using capillary zone electrophoresis and UV-Vis spectroscopy.
- Assessing cellular delivery and splicing correction of ASOs in integrin alpha v/beta 3 positive A375B3-Luc cells.
Main Results:
- Successful conjugation of RGD/iRGD peptides onto DPL was confirmed.
- RGD-DPL/ASO complexes demonstrated integrin receptor-mediated uptake in A375B3 cells.
- No significant cellular toxicity was observed with the RGD-DPL/ASO complexes.
Conclusions:
- RGD-peptide conjugated DPLs are effective carriers for antisense oligonucleotide delivery.
- The cellular delivery mechanism is dependent on integrin receptor interactions.
- This approach shows potential for targeted nucleic acid delivery with moderate efficiency and low toxicity.
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