ABSTRACT
The delivery of nucleic acids for therapeutic purposes must surmount multiple cellular barriers that restrict efficient gene delivery. Manipulation of the biology of the cell and association of various effectors with the nucleic acid or utilization of low-molecular-weight nucleic acids have been used to increase gene expression. An understanding of intracellular macromolecular transport requires a general familiarity of the structure and properties of the cytoplasm, which consists of a filamentous network embedded in an aqueous, gel-like matrix. Macromolecular transport mechanisms within the cytoplasmic space can be explained by diffusion and active transport associated with the cytoskeleton. Considerable effort has been directed to studying cytoplasmic diffusion of small inert particles that are microinjected into living cells. Nuclear accumulation is energy independent, and inhibitors of protein transport through the nuclear pore such as wheat germ agglutinin failed to diminish oligo accumulation in the nucleus. The interactions between oligos and nuclear structures can provide insight into why oligos are retained in the nucleus.
