Latest Publications

CD8+ T cells mediate protection against Zika virus induced by an NS3-based vaccine
November 2020
Zika virus (ZIKV) is associated with congenital malformations in infants born to infected mothers, and with Guillain-Barré syndrome in infected adults. Development of ZIKV vaccines has focused predominantly on the induction of neutralizing antibodies, although a suboptimal antibody response may theoretically enhance disease severity through antibody-dependent enhancement (ADE). Here, we report induction of a protective anti-ZIKV CD8+ T cell response in the HLA-B*0702 Ifnar1-/- transgenic mice using an alphavirus-based replicon RNA vaccine expressing ZIKV nonstructural protein NS3, a potent T cell antigen. The NS3 vaccine did not induce a neutralizing antibody response but elicited polyfunctional CD8+ T cells that were necessary and sufficient for preventing death in lethally infected adult mice and fetal growth restriction in infected pregnant mice. These data identify CD8+ T cells as the major mediators of ZIKV NS3 vaccine-induced protection and suggest a new strategy to develop safe and effective anti-flavivirus vaccines.
LUNAR®-CF, an aerosolized mRNA replacement Therapy for Cystic Fibrosis Lung Disease
October 2020
LUNAR®-CF is an aerosolized mRNA replacement therapy to treat Cystic Fibrosis (CF) Lung Disease, a therapeutic approach agnostic to a patient’s genotype. A healthy copy of the human CFTR mRNA is encapsulated into lipid nanoparticles (LUNAR®-hCFTR), aerosolized to patient’s airways using a vibrating mesh nebulizer to directly deliver a de novo human CFTR mRNA into epithelial cells. This human CFTR mRNA encodes a fully functional human CFTR protein that will be beneficial to facilitate mucociliary clearance and improve CF lung disease.

Publications

Publication
Journal/Date
Title
Overview
Publication
Journal/Date
November 2020
Title
CD8+ T cells mediate protection against Zika virus induced by an NS3-based vaccine
Overview
Zika virus (ZIKV) is associated with congenital malformations in infants born to infected mothers, and with Guillain-Barré syndrome in infected adults. Development of ZIKV vaccines has focused predominantly on the induction of neutralizing antibodies, although a suboptimal antibody response may theoretically enhance disease severity through antibody-dependent enhancement (ADE). Here, we report induction of a protective anti-ZIKV CD8+ T cell response in the HLA-B*0702 Ifnar1-/- transgenic mice using an alphavirus-based replicon RNA vaccine expressing ZIKV nonstructural protein NS3, a potent T cell antigen. The NS3 vaccine did not induce a neutralizing antibody response but elicited polyfunctional CD8+ T cells that were necessary and sufficient for preventing death in lethally infected adult mice and fetal growth restriction in infected pregnant mice. These data identify CD8+ T cells as the major mediators of ZIKV NS3 vaccine-induced protection and suggest a new strategy to develop safe and effective anti-flavivirus vaccines.
Publication
Journal/Date
October 2020
Title
Property Driven Design and Development of Lipids for Efficient Delivery of siRNA
Overview
Ionizable cationic lipids are critical components involved in nanoparticle formulations, which are utilized in delivery platforms for RNA therapeutics. While general criteria regarding lipophilicity and measured pKa in formulation are understood to have impacts on utility in vivo, greater granularity with respect to the impacts of the structure on calculated and measured physicochemical parameters and the subsequent performance of those ionizable cationic lipids in in vivo studies would be beneficial.
Publication
Journal/Date
September 2020
Title
A Single Dose of Self-Transcribing and Replicating RNA Based SARS-CoV-2 Vaccine Produces Protective Adaptive Immunity In Mice
Overview
A self-transcribing and replicating RNA (STARR™) based vaccine (LUNAR® 36 -COV19) has 37 been developed to prevent SARS-CoV-2 infection. The vaccine encodes an alphavirus-based 38 replicon and the SARS-CoV-2 full length spike glycoprotein.
Publication
Journal/Date
May 2020
Title
Lipid Nanoparticle Formulation Increases Efficiency of DNA-Vectored Vaccines/Immunoprophylaxis in Animals Including Transchromosomic Bovines
Overview
The use of nucleic acid as a drug substance for vaccines and other gene-based medicines continues to evolve. Here, we have used a technology originally developed for mRNA in vivo delivery to enhance the immunogenicity of DNA vaccines. We demonstrate that neutralizing antibodies produced in rabbits and nonhuman primates injected with lipid nanoparticle (LNP)-formulated Andes virus or Zika virus DNA vaccines are elevated over unformulated vaccine.
Publication
Journal/Date
May 2020
Title
Anti-HFRS Human IgG Produced in Transchromosomic Bovines Has Potent Hantavirus Neutralizing Activity and Is Protective in Animal Models
Overview
We explored an emerging technology to produce anti-Hantaan virus (HTNV) and anti-Puumala virus (PUUV) neutralizing antibodies for use as pre- or post-exposure prophylactics.
Publication
Journal/Date
January 2017
Title
Systemic delivery of factor IX messenger RNA for protein replacement therapy
Overview
Safe and efficient delivery of messenger RNAs for protein replacement therapies offers great promise but remains challenging. In this report, we demonstrate systemic, in vivo, nonviral mRNA delivery through lipid nanoparticles (LNPs) to treat a Factor IX (FIX)-deficient mouse model of hemophilia B.

Posters

Poster
Journal/Date
Title
Overview
Poster
Journal/Date
October 2020
Title
LUNAR®-CF, an aerosolized mRNA replacement Therapy for Cystic Fibrosis Lung Disease
Overview
LUNAR®-CF is an aerosolized mRNA replacement therapy to treat Cystic Fibrosis (CF) Lung Disease, a therapeutic approach agnostic to a patient’s genotype. A healthy copy of the human CFTR mRNA is encapsulated into lipid nanoparticles (LUNAR®-hCFTR), aerosolized to patient’s airways using a vibrating mesh nebulizer to directly deliver a de novo human CFTR mRNA into epithelial cells. This human CFTR mRNA encodes a fully functional human CFTR protein that will be beneficial to facilitate mucociliary clearance and improve CF lung disease.
Poster
Journal/Date
April 2019
Title
Challenges and Potential Solutions for Development of Successful Potency Assay in mRNA Therapeutics
Overview
mRNA Therapeutics require development of potency assays early during the pre-clinical stage. Conventional potency methods for protein biologic may not apply directly to mRNA therapeutic drug substance. Cell-based potency assays have to be carefully evaluated to make sure that the read-outs correspond to the actual potency of the drug substance and not an artifactual value. mRNAs can be evaluated for potency at level of protein expression (cell-free), cellular protein expression/stability and enzyme activity in vitro.
Poster
Journal/Date
April 2019
Title
mRNA Therapy For Ornithine Transcarbamylase Deficiency
Overview
LUNAR®-OTC treats patients suffering from ornithine transcarbamylse deficiency (OTCD) using mRNA to replace the wild-type human enzyme. OTCD is a rare metabolic disease in which the urea cycle cannot efficiently convert ammonia into urea. The efficacy of LUNAR®-OTC was evaluated in an animal model of OTCD ameliorating certain OTCD disease phenotypes in mice.
Poster
Journal/Date
October 2018
Title
LUNAR® selective delivery of nebulized mRNA into murine lung epithelial cells
Overview
LUNAR® lipid nanoparticles carrying the mRNA payload reaches the target cell, where it fuses with the plasma membrane forming an intracellular endosome. This endosomic particle undergoes a pH-mediated disruption that causes the breakdown of the biodegradable nanoparticle and the delivery of the mRNA into the cytoplasm.
Poster
Title
LUNAR-CF a mRNA Replacement Therapy for Cystic Fibrosis
Overview
Arcturus Therapeutics is a nucleic acid medicines company focused on developing RNA therapeutics to treat rare diseases. Our proprietary LUNAR® lipid-mediated delivery technology enables the efficient delivery of any mRNA into a variety of cell types and tissues, and can be optimized for multiple routes of administration.