Transport to the Perinuclear Region

DNA transport to the nuclear region of the cell is poorly characterized [10,75] but is believed to involve movement through endosomes [49,85] and diffusion of vectors [75]. Gene carriers that escape endosomes may need to diffuse through the cytoplasm to reach the nucleus [75]. Diffusion of gene carriers through the cytoplasm has not yet been investigated; however, a study of the diffusion of naked DNA segments using fluorescence recovery after photobleaching (FRAP) demonstrated that the cytoplasm can be a critical barrier to nuclear gene delivery [196]. The involvement of cytoskeletal elements in the intracellular transport of gene carriers is highly probable [118], especially since transport of endosomes requires such structures. Intracellular transport of liposomes has been shown to involve microtubules [197], since microtubule depolymerization by nocodazole and stabilization by taxol both prevented perinuclear accumulation of the carriers. Our lab showed that PEI/DNA nanocomplexes also utilized microtubules for rapid transport to the perinuclear region in Cos-7 cells [118].

The method by which a DNA vector is trafficked intracellularly may have important implications on the efficiency of gene delivery. If DNA vectors are trafficked to sites far from the nucleus, gene delivery will be hindered by the diffusion-limited cytoplasm. PEI and polylysine are both cationic polymers with the ability to condense DNA; however, they have been shown to traffic to different intracellular destinations [198] and result in different transfection efficiencies [199]. In addition, particles of different chemistries were routed differently by the same cell type [200]. Understanding the intracytoplasmic transport of DNA vectors will be critical if higher-efficiency vectors are to be engineered.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

Get My Free Ebook

Post a comment