2008 NSTI Nanotechnology Conference and Trade Show - Nanotech 2008 - 11th Annual

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TechConnect Summit
Clean Technology 2008

Pharmacokinetic Optimization of Phage Particles for Gene-Delivery

A. Baird, D. Larocca
University of California San Diego Medical Center, US

gene delivery, evolution, ligand-receptor internalization, vectors, pharmacokinetics

We previously reported that single stranded bacteriophage, when appropriately re-engineered, can be used for gene delivery to mammalian cells. The process is receptor specific and concentration and time dependent. Remarkably, we also observe that the DNA that phage deliver is long lived and that gene expression from its DNA can be sustained for several months, even without drug selection. In many ways, phage nanoparticles could be ideal vectors for gene delivery. First, they are readily manufacturable compared to mammalian viruses and can be grown to relatively high titer. Furthermore, their bacterial hosts are amenable to genetic optimization for improved particle assembly, increased yield and defined specifications. Second, these nanoparticles can be genetically modified through rational design for altered behavior inside target cells (e.g. nuclear localization), in biological fluids (e.g. blood) and in its formulation before delivery (e.g. excipient). Third, unlike mammalian viruses, peptide display and reiterative selection can be used to genetically select particles with characteristics that defy rational design: biodistribution, pharmacokinetics and immunogenicity. Here we review progress towards creating a primordial phage nanoparticle that is pharmacokinetically optimized with the express purpose of therapeutic gene delivery.

Nanotech 2008 Conference Program Abstract