Title:Membrane Fusion Mediated Targeted Cytosolic Drug Delivery Through scFv Engineered Sendai Viral Envelopes
VOLUME: 15 ISSUE: 4
Author(s):M. Kumar, P. Mani, P. Pratheesh, S. Chandra, M. Jeyakkodi, P. Chattopadhyay, D.P. Sarkar and S. Sinha
Affiliation:(S. Sinha) National Brain Research Centre, NH-8, Manesar, Gurgaon, Haryana, PIN- 122051, India.
Keywords:F-protein, F-virosome, placental alkaline phosphatase, scFv, Sendai virosome, targeted drug delivery.
Abstract:Antibody targeted cytoplasmic delivery of drugs is difficult to achieve as antigen-antibody interaction
results in the payload being directed to the endosomal compartment. However, Sendai viral envelopes can
bring about cytoplasmic delivery due to F-protein mediated membrane fusion. In this study we have generated
and fused a recombinant scFv directed to the onco-fetal antigen, the Placental isozyme of Alkaline
Phosphatase (PAP) with the trans-membrane and part of the cytoplasmic domain of the Sendai F protein
(FTMC). Reconstituted virosomes, having both the fusion protein as well as the native F-protein were able to
specifically bind and deliver drugs to PAP expressing cells. About 75% of the delivery was cytoplasmic in
nature. Hence, this immuno-virosome, which is devoid of the comparatively more toxic HN protein, has the
novel ability to combine specific antibody mediated targeting with cytoplasmic delivery. The scFv ensured
specific binding to PAP expressing cells, without cross reacting with the other isozymes of alkaline
phosphatase. The advantages of cytoplasmic delivery would include reduced degradation and lowered
immunogenicity of the payload and carrier. The ubiquitous expression of PAP on a variety of cancers like
seminoma, choriocarcinoma, cervical and breast cancers also suggests its potential usefulness in a number of
malignancies.
