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Aug 20, 2024

Cytosolic RNA depletion by polymeric nanoparticles

Life Sciences, Oncology

  • Mucin nanoparticles cross-linked with anti-miRNA oligonucleotides
  • Treating systemic diseases associated with increased cellular RNA levels
  • Depletion of miRNA-21 reduced tumor growth in vivo by 50%

Your contact

Linda Keil

E-Mail:
lkeil@baypat.de
Phone:
+49 (0) 89 5480177 – 30
Reference Number:
B83117

Challenge

MicroRNAs (miRNAs) are small, double-stranded RNAs that exert fine-tuned, sequence-specific regulation of the cellular transcriptome. While a single miRNA regulates hundreds of mRNAs, each mRNA molecule is commonly regulated by only a few miRNAs that bind to complementary sequences at 3'-untranslated regions to trigger the mechanism of RNA interference. Unfortunately, dysregulated miRNAs play a critical role in many diseases. The over-expression of certain miRNAs plays a role in a number of pathogenic processes, such as in the development of cancer. But also in other diseases, such as atherosclerosis, type II diabetes, obesity, viral infections and cardiovascular
diseases, miRNA might play an important role. Overexpression of e.g., miR21 in cancer is responsible for increases in colony formation and survival rate of tumor cells.
A challenge for miRNA therapeutics is to maintain the stability and consistency of miRNAs in circulation. Naked miRNAs are degraded by nucleases within seconds or are rapidly removed by renal excretion. Thus, suitable delivery systems are needed that stabilise the antisense DNA, allow efficient uptake by the cells, while avoiding off-targets. They should also be adjustable so they can deplete any target RNA.

Innovation

The invention describes nanoparticles (NP) composed of biopolymer-DNA conjugates that have the ability to bind and inactivatecytosolic miRNA in cells. Two types of NPs are described: (1) 'sponge' NPs, which bind miRNA in a condensed state, as the binding sites are exposed and (2) transient NPs, which open in the cell after initial contact with the miRNA and can bind further miRNAs. The transient NP can act as a targeted drug delivery system, releasing a drug only upon contact with a specific trigger DNA sequence. The design of the DNA sequences that stabilise the NPs can be freely adapted to any cytosolic RNA target. It was shown that these NPs were successfully taken up, were able to escape from endosomes and were effective in silencing miRNA.

Commercial Opportunities

  • Mucin nanoparticles cross-linked with anti-miRNA oligonucleotides show high selectivity and efficient uptake by target cells
  • Treating systemic diseases associated with increased cellular RNA levels
  • Depletion of miRNA-21 reduced tumor growth in vivo by 50%
  • Currently demonstrated with mucins, but any other polymer can be used

Development Status

TRL Level 5: Technology validated in relevant environment

References

Interested? Get in touch!

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