3 research outputs found
Recommended from our members
Next-generation of targeted AAVP vectors for systemic transgene delivery against cancer
Bacteriophage (phage) have attractive advantages as delivery sys-tems compared to mammalian viruses, but have been consideredpoor vectors because they lack evolved strategies to confrontand overcome mammalian cell barriers to infective agents. Wereasoned that improved efficacy of delivery might be achievedthrough structural modification of the viral capsid to avoid pre-and post-internalization barriers to mammalian cell transduction.We generated multifunctional hybrid AAV/phage (AAVP) particlesto enable simultaneous display of targeting ligands on the phage’sminor pIII proteins and also degradation-resistance motifs on thevery numerous pVIII coat proteins. This genetic strategy of directedevolution, bestows a next-generation of AAVP particles that fea-ture resistance to fibrinogen adsorption or neutralizing antibodies,and ability to escape endolysosomal degradation. This results insuperior gene transfer efficacyin vitroand also in preclinicalmouse models of rodent and human solid tumors. Thus, the uniquefunctions of our next-generation AAVP particles enable improvedtargeted gene delivery to tumor cells
Recommended from our members
Next-generation of targeted AAVP vectors for systemic transgene delivery against cancer
Bacteriophage (phage) have attractive advantages as delivery systems compared with mammalian viruses, but have been considered poor vectors because they lack evolved strategies to confront and overcome mammalian cell barriers to infective agents. We reasoned that improved efficacy of delivery might be achieved through structural modification of the viral capsid to avoid pre- and postinternalization barriers to mammalian cell transduction. We generated multifunctional hybrid adeno-associated virus/phage (AAVP) particles to enable simultaneous display of targeting ligands on the phage's minor pIII proteins and also degradation-resistance motifs on the very numerous pVIII coat proteins. This genetic strategy of directed evolution bestows a next-generation of AAVP particles that feature resistance to fibrinogen adsorption or neutralizing antibodies and ability to escape endolysosomal degradation. This results in superior gene transfer efficacy in vitro and also in preclinical mouse models of rodent and human solid tumors. Thus, the unique functions of our next-generation AAVP particles enable improved targeted gene delivery to tumor cells