Nuclear uptake

DNA-binding mechanism that does not involve DNA damage or disruption of chromosomal integrity [86]. 

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Mistry P, Mastri C, Fowler BA. 1986. Influence of metal ions on renal cytosolic lead-binding proteins and nuclear uptake of lead in the kidney. Biochem Pharmacol 35 711-713. 

Intracellular pathways after escape from the endolysosomal system into the cytosol are less clear. Obvious bottlenecks include, in the case of gene transfer (pDNA delivery), cytosolic transport to the perinuclear area, nuclear uptake, and nuclear presentation of the pDNA to the transcriptional machinery in bioactive form. In the case of siRNA (or mRNA and some other nucleic acids such as oligonucleotides), cytosolic accessibility for the required function is essential. Besides cytosolic transport [176, 177] and the nuclear import of large nucleic acid molecules [178-180], incorporation of functional nuclear import peptide domains has been evaluated [181-186]. Another bottleneck, nucleic acid unpackaging [187], i.e., partial or complete dissociation from the polymeric carrier, which is required for biological accessibility of the delivered nucleic acid, will be discussed in Sect. 3.3. 

Zupan, J.R., Citovsky, V. and Zambryski, P. (1996) Agrobacterium VirE2 protein mediates nuclear uptake of single-stranded DNA in plant cells. Proc. Natl. Acad. Sci. USA, 93, 2392-2397. 

Figure 6 Intracellular barriers to gene delivery include cellular uptake, intracellular transport, endosome escape, vector unpacking, and nuclear uptake. The gene carrier illustrated here has targeting moieties on the vector surface that are specific for cell surface receptors. The dotted arrow represents the prerequisite step of bypassing physiological barriers of the lung, such as the mucosal layer, and reaching the target cell surface.

Figure 72.3 Typical thyroid pertechnetate nuclear uptake in type I amiodarone-induced TTX, which is often patchy. The white, closed circle marks the sternal notch.

Figure 72.4 Typical thyroid pertechnetate nuclear uptake in type II amiodarone-induced TTX. Typically, there is no uptake due to the acute inflammatory process, which discharges all the THs, resulting in an absent uptake. The white arrows point to the salivary glands for comparison of uptake.

Nuclear uptake will be facilitated by viral nuclear localization signal (NLS) peptides... 

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