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Vector Engineering for Cell and Gene Therapy
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Progress in gene therapy has been hampered by the absence of a suitable delivery vector that is both easy to produce and delivers genetic payloads efficiently and specifically to the targeted disease cells. Cell-targeting proteins, primarily monoclonal antibodies, already exist in abundance but there is currently no robust and reproducibly effective way to functionalize viral vectors with these proteins. In the case of antibodies, non-covalent approaches to incorporate antibody onto a lentivirus surface leaves the linkage vulnerable to interference from serum immunoglobulins in immune-competent individuals. This dissertation focuses on enabling facile reprogramming of lentiviral vectors to deliver genetic payloads to specific cell types through in vitro covalent functionalization with cell-binding proteins. Two covalent-bond forming protein-protein pairs were explored to conjugate a HER2-binding protein to lentivirus pseudotyped with a binding-deficient, fusion-competent Sindbis virus envelope protein. Both the strategies resulted in functionalization of lentivirus and the titers were significantly higher compared to the naked virus. A receptor dependent retargeting was observed with functionalized virions. Lastly, the covalent bond was observed to be stable during prolonged dialysis and in presence of serum complement. A chemical conjugation approach was successfully exploited to functionalize the virions with an antibody fragment. In another project, we aim to develop a new platform technology, building upon the antibody-guided chicken vaccine technology and the single emulsion technology, for iii the discovery of chicken IgY antibodies against target cancer antigens. The antibody-guided chicken vaccine technology approach was successfully developed to generate an immune response in chickens against the target cancer antigen.
Single chain variable fragment
Kasaraneni, Nagarjun (2017). Vector Engineering for Cell and Gene Therapy. Doctoral dissertation, Texas A & M University. Available electronically from