Intracellular delivery of antibodies by chimeric Sesbania mosaic virus (SeMV) virus like particles.

Ambily Abraham,Ashutosh Gulati,Pavithra Mukunda,Handanahal S Savithri,Anjali A Karande,Sathyabalan Murugesan,Mathur R N Murthy,Usha Natraj

doi:10.1038/srep21803

Abstract

The therapeutic potential of antibodies has not been fully exploited as they fail to cross cell membrane. In this article, we have tested the possibility of using plant virus based nanoparticles for intracellular delivery of antibodies. For this purpose, Sesbania mosaic virus coat protein (CP) was genetically engineered with the B domain of Staphylococcus aureus protein A (SpA) at the βH-βI loop, to generate SeMV loop B (SLB), which self-assembled to virus like particles (VLPs) with 43 times higher affinity towards antibodies. CP and SLB could internalize into various types of mammalian cells and SLB could efficiently deliver three different monoclonal antibodies–D6F10 (targeting abrin), anti-α-tubulin (targeting intracellular tubulin) and Herclon (against HER2 receptor) inside the cells. Such a mode of delivery was much more effective than antibodies alone treatment. These results highlight the potential of SLB as a universal nanocarrier for intracellular delivery of antibodies.

Highlights

Antibody based therapy is a successful protein targeting strategy in medicine that can disrupt protein-protein interactions or inhibit signalling pathways[1,2]
Bionanoparticles are being increasingly investigated as nanocarriers, as compared to synthetic nanoparticles owing to their target specificity and biocompatibility with the host
Plant virus nanoparticles have been extensively explored as protein cages for intracellular delivery[24,25]

Summary

Introduction

Antibody based therapy is a successful protein targeting strategy in medicine that can disrupt protein-protein interactions or inhibit signalling pathways[1,2]. Some of the VNPs have been genetically engineered or chemically modified with Staphylococcus aureus protein A (SpA) or their sub-domains like B, Z or Z33, that can bind to IgGs11, to create chimeric VNPs12,13. In most instances, such chimeras have been used for increased sensitivity of bioassays, cellular targeting and increased immunogenicity. SLB was able to efficiently deliver all the three antibodies inside mammalian cells and most importantly, the antibodies retained their functionality inside cells These results demonstrate that SLB can be a universal antibody delivering agent that can enhance the efficacy of therapeutic antibodies targeted to surface antigens and pave way for delivering other antibodies that target potential intracellular targets

Methods

Results

Conclusion