Imperial College London


Faculty of MedicineDepartment of Infectious Disease

Chair in Mucosal Infection and Immunity



+44 (0)20 7594 5206r.shattock




453Wright Fleming WingSt Mary's Campus






BibTex format

author = {Blakney, AK and McKay, PF and Yus, BI and Aldon, Y and Shattock, RJ},
doi = {10.1038/s41434-019-0095-2},
journal = {Gene Therapy},
pages = {363--372},
title = {Inside out: optimization of lipid nanoparticle formulations for exterior complexation and in vivo delivery of saRNA},
url = {},
volume = {26},
year = {2019}

RIS format (EndNote, RefMan)

AB - Self-amplifying RNA (saRNA) is a promising biotherapeutic tool that has been used as a vaccine against both infectious diseases and cancer. saRNA has been shown to induce protein expression for up to 60 days and elicit immune responses with lower dosing than messenger RNA (mRNA). Because saRNA is a large (~9500 nt), negatively charged molecule, it requires a delivery vehicle for efficient cellular uptake and degradation protection. Lipid nanoparticles (LNPs) have been widely used for RNA formulations, where the prevailing paradigm is to encapsulate RNA within the particle, including the first FDA-approved small-interfering siRNA therapy. Here, we compared LNP formulations with cationic and ionizable lipids with saRNA either on the interior or exterior of the particle. We show that LNPs formulated with cationic lipids protect saRNA from RNAse degradation, even when it is adsorbed to the surface. Furthermore, cationic LNPs deliver saRNA equivalently to particles formulated with saRNA encapsulated in an ionizable lipid particle, both in vitro and in vivo. Finally, we show that cationic and ionizable LNP formulations induce equivalent antibodies against HIV-1 Env gp140 as a model antigen. These studies establish formulating saRNA on the surface of cationic LNPs as an alternative to the paradigm of encapsulating RNA.
AU - Blakney,AK
AU - McKay,PF
AU - Yus,BI
AU - Aldon,Y
AU - Shattock,RJ
DO - 10.1038/s41434-019-0095-2
EP - 372
PY - 2019///
SN - 0969-7128
SP - 363
TI - Inside out: optimization of lipid nanoparticle formulations for exterior complexation and in vivo delivery of saRNA
T2 - Gene Therapy
UR -
UR -
UR -
VL - 26
ER -