Acuitas scientists, in collaboration with other researchers, have published extensively on LNP development and characterization.
Pardi et al. (2017b) “Administration of nucleoside-modified mRNA encoding broadly neutralizing antibody protects humanized mice from HIV-1 challenge” Nature Communications doi:10.1038/ncomms14630
In a collaboration with Dr. Drew Weissman at the University of Pennsylvania it was shown that a mRNA-LNP encoding the anti-HIV-1 antibody VRC01 protected humanized mice from an intravenous HIV-1 challenge in a dose-dependent manner.
Pardi et al. (2017a) “Zika virus protection by a single low-dose nucleoside-modified mRNA Vaccination” Nature doi:10.1038/nature21428
In a collaboration with academic researchers including Dr. Drew Weissman at the University of Pennsylvania it was shown that single low-dose immunization with mRNA-LNP encoding the pre-membrane and envelope (prM-E) glycoproteins of a Zika virus strain responsible for the 2013 outbreak elicited potent, durable and protective neutralizing antibody responses in animals.
Pardi et al. (2015) “Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes” J Controlled Release doi:10.1016/j.jconrel.2015.08.007
In collaboration with Dr. Drew Weissman and his research team at the University of Pennsylvania efficient protein translation was demonstrated in mice following dosing of modified mRNA encapsulated in Acuitas LNP carriers via various routes of administration.
Thess et al. (2015) “Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals” Mol Ther doi: 10.1038/mt.2015.103.
In collaboration with CureVac scientists we demonstrate the ability of sequence-engineered mRNAs delivered in Acuitas LNP carriers to provide high levels of protein expression (erythropoietin) in large animal species with attendant pharmacological benefits.
Mui et al. (2013) “Influence of polyethylene glycol lipid desorption rates on pharmacokinetics and pharmacodynamics of siRNA lipid nanoparticles” Mol Ther Nucleic Acids. 2013. Epub 2013 Dec 17.
In this paper, Acuitas scientists report on the identification and characterization of the key role of polyethylene glycol lipids in the activity of lipid nanoparticle systems for nucleic acid delivery.
Maier et al. (2013) “Biodegradable lipids enabling rapidly eliminated lipid nanoparticles for systemic delivery of RNAi therapeutics” Mol Ther. 2013. Epub 2013 June 25.
This paper describes new classes of biodegradable cationic lipids with enhanced safety profiles and pharmaceutical properties.
Jayaraman et al. (2012) “Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo” Angew Chem Int Ed Engl. 2012 Aug 20;51(34):8529-33. doi: 10.1002/anie.201203263. Epub 2012 Jul 10.
In this paper Acuitas scientists describe key structure-activity relationships (SAR) that define the potency of different cationic lipids for nucleic acid delivery.
Semple et al. (2010) “Rational design of cationic lipids for siRNA delivery” Nat Biotechnol. 2010 Feb;28(2):172-6. doi: 10.1038/nbt.1602. Epub 2010 Jan 17.
This paper describes a rational design approach taken to identify more potent cationic lipids for use in LNP delivery systems.
Akinc et al. (2010) “Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms” Mol Ther. 2010 Jul;18(7):1357-64. doi: 10.1038/mt.2010.85. Epub 2010 May 11.
This publication describes the importance of ApoE-mediated uptake of LNP into cells.
Tam YY, Chen S, Zaifman J, Tam YK, Lin PJ, Ansell S, Roberge M, Ciufolini MA, Cullis PR. “Small molecule ligands for enhanced intracellular delivery of lipid nanoparticle formulations of siRNA”. Nanomedicine. 2013 Jul;9(5):665-74. doi: 10.1016/j.nano.2012.11.006. Epub 2012 Dec 6.
This publication describes the use of small molecule ligands to enhance cellular uptake of siRNA-LNP.
Leung AK, Hafez IM, Baoukina S, Belliveau NM, Zhigaltsev IV, Afshinmanesh E, Tieleman DP, Hansen CL, Hope MJ, Cullis PR. “Lipid nanoparticles containing siRNA synthesized by microfluidic mixing exhibit an electron-dense nanostructured core” J Phys Chem C Nanomater Interfaces. 2012 Aug 30;116(34):18440-18450. Epub 2012 Jul 18.
The macromolecular structure of siRNA-LNP prepared by a microfluidic mixing process is described in this publication.
Lee JB, Zhang K, Tam YY, Tam YK, Belliveau NM, Sung VY, Lin PJ, LeBlanc E, Ciufolini MA, Rennie PS, Cullis PR. “Lipid nanoparticle siRNA systems for silencing the androgen receptor in human prostate cancer in vivo. Int J Cancer. 2012 Sep 1;131(5):E781-90. doi: 10.1002/ijc.27361. Epub 2012 Jan 3.
This publication describes the use of siRNA-LNP to knockdown the androgen receptor in murine studies.
Belliveau NM, Huft J, Lin PJ, Chen S, Leung AK, Leaver TJ, Wild AW, Lee JB, Taylor RJ, Tam YK, Hansen CL, Cullis PR. “Microfluidic synthesis of highly potent limit-size lipid nanoparticles for in vivo delivery of siRNA. Mol Ther Nucleic Acids. 2012 Aug 14;1:e37. doi: 10.1038/mtna.2012.28
This paper describes the use of microfluidic techniques to prepare siRNA-LNP.
Basha G, Novobrantseva TI, Rosin N, Tam YY, Hafez IM, Wong MK, Sugo T, Ruda VM, Qin J, Klebanov B, Ciufolini M, Akinc A, Tam YK, Hope MJ, Cullis PR. “Influence of cationic lipid composition on gene silencing properties of lipid nanoparticle formulations of siRNA in antigen-presenting cells” Mol Ther. 2011 Dec;19(12):2186-200. doi: 10.1038/mt.2011.190. Epub 2011 Oct 4.
The potency of LNP with differing cationic lipids in silencing cellular targets in vitro is described in this publication.