Background: Successful gene delivery requires overcoming both systemic and intracellular
obstacles before the nucleic acid cargo can successfully reach its tissue and subcellular target location.
Materials & Methods: Non-viral mechanisms to enable targeting while avoiding off-target delivery
have arisen via biological, chemical, and physical engineering strategies.
Discussion: Herein we will discuss the physical parameters in particle design that promote tissue- and
cell-targeted delivery of genetic cargo. We will discuss systemic concerns, such as circulation, tissue
localization, and clearance, as well as cell-scale obstacles, such as cellular uptake and nucleic acid
Conclusion: In particular, we will focus on engineering particle shape and size in order to enhance delivery
and promote precise targeting. We will also address methods to program or change particle
shape in situ using environmentally triggered cues.