Acuitas specializes in the development of systemic delivery systems for molecular therapeutics based on lipid nanoparticles (LNP). Our scientists have developed LNP carriers for delivery of nucleic acids including siRNA, mRNA and antisense oligonucleotides. Such carriers can be administered systemically and protect the encapsulated nucleic acid from nuclease degradation in the circulation. We have shown that the ionizable cationic lipid component critically determines the potency of LNP-therapeutics. Using a rational design approach we have synthesized over 200 novel cationic lipids and screened these in an in vivo model system (Semple et al., Nat Biotechnol. 2010). We have also undertaken biophysical characterization of such novel LNP systems and conducted correlation analyses to determine which structural and biophysical properties of the cationic lipid are critical for activity. This rational design and screening approach has resulted in the identification of LNP compositions with greatly improved potency and therapeutic index (Jayaraman et al., Angew Chem Int Ed Engl. 2012; Maier et al. Mol Ther. 2013). Further, mechanism of action studies have established that LNP compositions optimized for nucleic acid delivery to hepatocytes bind the lipoprotein ApoE in the circulation and this bound ApoE then facilitates receptor-mediated uptake into the target cells (Akin et al., Mol Ther. 2009).

Acuitas is developing LNP technology under limited license from Tekmira Pharmaceuticals Corporation.

Technology Focus

• Lipid nanoparticles for intracellular delivery of molecular therapeutics – primarily nucleic acids
• Pharmaceutical applications:
  • Protein replacement therapeutics (mRNA or plasmid delivery)
  • Protein knockdown therapeutics (antisense)