813. Targeted Delivery of Biotinylated Compounds by Lodavin™, LDL-Receptor – Avidin Fusion Protein, Expressing Lentivirus
Authors: Hanna P. Lesch, Jere T. Pikkarainen, Thomas Wirth, Minna U. Kaikkonen, Olli H. Laitinen, Kari J. Airenne, Seppo Yla- Herttuala
Journal: Molecular Therapy (2006)

Targeted drug delivery is a fascinating option to maximize the beneficial effects of the used drug molecule in the correct target tissue or to diminish the possible side effects of toxic drug compounds in erroneous tissues. Conventional approaches for targeting in gene therapy are vector pseudotyping and the use of tissue specific promoters. An alternative approach would be to modify the target cells/tissues so that they contain an artificial targeting receptor. For this aim our group has recently constructed Lodavin™, a fusion protein consisting of cytoplasmic and transmembrane domains of LDL receptor and avidin, a specific high affinity biotin-binding protein from chicken. The fact that humans and other mammals do not contain a counterpart for avidin makes Lodavin™ a promising artificial receptor for the targeted drug delivery. In addition, biotinylation of drug molecules is considerably easy. In the present study we constructed HIV-1 based Lodavin™ vector: Lodavin™- lenti. The Lodavin™-lenti transduced cells show stable expression of Lodavin™ on their cell membranes.Lodavin™ expression was detected from transduced cells by western blotting and confocal microscopy. Lodavin™-lenti was studied in vivo by direct injection of mouse subcutaneous tumors wherefrom it was detected by immuno-histochemistry.Our results demonstrate that Lodavin™-lenti presents a viable alternative for the targeted drug delivery. It drives a long term expression of the Lodavin™ on the membranes of transduced cells, which allows development of several ex vivo and in vivo targeting approaches. Besides targeted drug delivery, imaging of the transduced cells with Lodavin™-lenti should be possible from intact animals using several non-invasive methods like SPECT and MRI. Targeted drug delivery is a fascinating option to maximize the beneficial effects of the used drug molecule in the correct target tissue or to diminish the possible side effects of toxic drug compounds in erroneous tissues. Conventional approaches for targeting in gene therapy are vector pseudotyping and the use of tissue specific promoters. An alternative approach would be to modify the target cells/tissues so that they contain an artificial targeting receptor. For this aim our group has recently constructed Lodavin™, a fusion protein consisting of cytoplasmic and transmembrane domains of LDL receptor and avidin, a specific high affinity biotin-binding protein from chicken. The fact that humans and other mammals do not contain a counterpart for avidin makes Lodavin™ a promising artificial receptor for the targeted drug delivery. In addition, biotinylation of drug molecules is considerably easy. In the present study we constructed HIV-1 based Lodavin™ vector: Lodavin™- lenti. The Lodavin™-lenti transduced cells show stable expression of Lodavin™ on their cell membranes. Lodavin™ expression was detected from transduced cells by western blotting and confocal microscopy. Lodavin™-lenti was studied in vivo by direct injection of mouse subcutaneous tumors wherefrom it was detected by immuno-histochemistry. Our results demonstrate that Lodavin™-lenti presents a viable alternative for the targeted drug delivery. It drives a long term expression of the Lodavin™ on the membranes of transduced cells, which allows development of several ex vivo and in vivo targeting approaches. Besides targeted drug delivery, imaging of the transduced cells with Lodavin™-lenti should be possible from intact animals using several non-invasive methods like SPECT and MRI.