nanoVAST: a novel, non- viral LNP for precision payload delivery of genome editors and other cargo

Cell-specific cargo delivery is a key remaining problem in the field of RNA-based therapeutics.

Thus far, delivery has relied on lipid nanoparticles (LNPs) which encapsulate RNA with high efficiency, but broadly lack in specificity.

Viral vectors are currently the only FDA approved tissue-specific cargo delivery option, with specificity being the result of manipulation of outer capsid proteins.

However, viral systems are also associated with drawbacks such as oncogenicity, antigenicity and pre-existing immunity to the viral carrier itself.

The ideal carrier system would involve LNP-efficient cargo encapsulation together with specific targeting in the absence of oncogenicity or immunogenicity.

DKFZ and Panosome GmbH have together developed this exact particle – the nanoVAST: a patented vesicular phospholipid bilayer densely decorated with a single protein that can be fused to a targeting molecule of interest through specific, efficient, and separately patented chemistry.

Importantly, the attachment of the targeting component relies on a coupling of the vesicle to the targeting moiety, rather than a genetic manipulation of the carrier itself (as is the case with viral vectors), giving this system an unparalleled level of versatility.

Additionally, our vesicular system is inherently fusogenic with target membranes, thus permitting cargo delivery directly to the cytoplasm and avoiding the reliance on the incredibly inefficient “endosomal escape” mechanism that plagues LNPs (it is estimated that conventional LNPs only deliver approximately 1% or less of their payload into the cytoplasm).

This ERC PoC proposes to use the nanoVAST particle to (a) deliver specific RNA cargo to CD19+ B cells; (b) transport within the cells this cargo to the endogenous RNA editing machinery and (c) functionally alter the surface of the targeted cells.

Through the PoC we aim to accelerate nanoVAST, our precision payload delivery system, towards direct clinical applications.