Numerous first generation phosphorothioates (PS) and their derivatives have shown promise targeting mRNA for therapeutic applications and also gained market approval for their use as a drug. However, PS have not been explored for targeting microRNAs (miRNAs or miRs). In particular, efficient delivery remains a critical cog in PS-based antimiR applications. In this study, we tested and characterized a series of poly-lactic-co-glycolic-acid (PLGA) polymers of different molecular weights that can encapsulate the optimum amount of antimiR-155 PS with uniform morphology and surface charge density. We found that nuclear localization sequence substantially increases loading of antimiR-155 PS in PLGA nanoparticles. Further, in a battery of cell culture studies, we confirmed that PLGA nanoparticles encapsulated nuclear localization sequence/antimiR-155 PS combination undergoes significant intracellular delivery and results in reduced expression of miR-155. In conclusion, we successfully demonstrate the feasibility and promise of optimized PLGA nanoparticles based PS delivery in combination with nuclear localization sequence for antimiRs based therapeutics.
Electronic supplementary material
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Background:
Peptide nucleic acids (PNAs) belong to the next generation of synthetic nucleic acid
analogues. Their high binding affinity and specificity towards the target DNA or RNA make them the reagent of
choice for gene therapy-based applications.
Objective:
To review important gene therapy based applications of regular and chemically modified peptide nucleic
acids in combination with nanotechnology.
Method:
Selective research of the literature.
Results:
Poor intracellular delivery of PNAs has been a significant challenge. Among several delivery strategies
explored till date, nanotechnology-based strategies hold immense potential. Recent studies have shown that advances
in nanotechnology can be used to broaden the range of therapeutic applications of PNAs. In this review,
we discussed significant advances made in nanoparticle-based on PLGA polymer, silicon, oxidized carbon and
graphene oxide for the delivery of PNAs.
Conclusion:
Nanoparticles delivered PNAs can be implied in diverse gene therapy based applications including
gene editing as well as gene targeting (antisense) based strategies.
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