Aromatic self-assembling polyethylenimines as effective siRNA delivery reagents

CONECTUS ALSACE



28 Juillet 2015

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Fields

Biology / Medical

Sectors

Health
  • New class of cationic self-assembling polymers exhibiting a pH-sensitive dissolution switch for the formation of stable siRNA polyplexes outside the cell and the release of oligonucleotides in the endosome.
  • High potential agent for systemic in vivo delivery

TECHNOLOGY

  • Self-assembling polyplexes with efficient endosomal escape
  • Polyplex can be made stable with 70 nm diameter, Zeta = + 35 mV, compatible for iv injection
  • No aggregation in serum, low hemolytic and cytotoxic profile
  • Stability after incubation in 100 % serum and at various N/P ratio
  • Greater than 90% reduction in target mRNA levels by target siRNA at concentrations <10 nM in media containing 10% serum
  • Less than 10% reduction in target mRNA levels by control siRNA at concentrations <10 nM in media containing 10% serum
  • >15-fold window between target gene silencing IC50 and IC50 for reduction in viability
  • Demontrated activity in multiple cell lines (i.e. U87, A549, HeLa, HuH7, BHK-21) and different target genes

APPLICATIONS

  • Versatile siRNA delivery reagent extensible to miRNA, protein and antibodies
  • in vitro, ex-vivo and in vivo application

INNOVATION ADVANTAGES

  • Self-aggregating PEI derivatives with pH-sensitive disassembly switch
  • Versatile delivery reagent for bioactive molecules as siRNA, miRNA and proteins
  • Efficient in vitro and in vivo
  • An easy procedure (« mix and go ») and stable formulations
  • Low hemolytic and low toxicity profile
  • Low production cost and ease of synthetic scale-up

 

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