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.
Keywords: F-protein, F-virosome, placental alkaline phosphatase, scFv, Sendai virosome, targeted drug delivery.
Related Books
Industrial Applications of Soil Microbes
Industrial Applications of Soil Microbes
Algal Biotechnology for Fuel Applications
Biopolymers Towards Green and Sustainable Development
Environmental Microbiology: Advanced Research and Multidisciplinary Applications
Biomarkers in Medicine
Industrial Applications of Soil Microbes
Sustainable Utilization of Fungi in Agriculture and Industry
Myconanotechnology: Green Chemistry for Sustainable Development
Bioluminescent Marine Plankton
32
3
2