Selective accumulation is a process where drugs are uniformly distributed in a s

Question

Selective accumulation is a process where drugs are uniformly distributed in a specific body tissue of interest. There are two ways by which the challenge of selective accumulation can be overcome. They are, 1) Cellular Internalization and 2) Endosomal Escape.

To deliver a DNA as a therapeutic, the DNA must be selectively accumulated into the nucleus because the transcriptional machinery occurred in the nucleus. As an example, it is stated that around 30 years ago, to express Thymidine Kinase in Thymidine Kinase deficient cells, the gene of Thymidine Kinase is incorporated in a plasmid DNA and the construct directly transferred into the nucleus of the gene-deficient cell by the uses of Microinjection. Microinjection is gene transfer tool where a DNA can directly transfer into a host without any genetic engineer or any gene transfer vector. The success rate of transferring the thymidine kinase gene is checked by H3 tagged thymidine, where H3 tagged where the Thymidine is present and detected with the help of autoradiography. As a result, it is detected that 50-100% of the nuclei, which are deficient in thymidine kinase, are now incorporated with thymidine kinase by selective accumulation process.

In this process around >1000 cells failed to incorporate the plasmid DNA contains the Thymidine Kinase gene, because of the nuclear envelope of these cells. They are too rigid that the microinjection failed to transfect those cells. Thus Nuclear uptake of the synthetic Gene of Interest(GOI) is the rate-limiting step or the slowest step of 'Selective Accumulation' process.

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???? ?? Selective accumulation?? ??? ??? Thus Nuclear uptake of the synthetic Gene of Interest(GOI) is the rate-limiting step or the slowest step of 'Selective Accumulation' process.?? ???? ?? Thus Nuclear? uptake ? ?????

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Explanation / Answer

Selective accumulation basically reers to. Process where any xenobiotic substance or drug is selectively uptaken by the target tissues. This selective uptanke of drug is facilitated by some specialized transporter proteins of the target cell or some cell specific transportation process. The nuclear uptake of synthetic gene of interest is rate limiting step of selective accumulation because nucleus of a eukaryotic cell is a double membrane layer cell organelle which allows only selective molecule to enter inside the nucleus of the cell that has Nuclear Localization signal (NLS) present on it. If this NLS is not present on the molecules that needs to be transported inside the nucleus of the cell through nuclear pore complex present on nuclear membrane. Even if the gene of interest gains entry inside the nucleus of the cell it is very difficult to incorporate this foreign DNA molecule into the host genome. The nuclear uptake basically refers to the process of successful uptake of the synthetic gene of interest by the nucleus of the cell and successful incoporation into the genome of an organism DNA molecule which can take place through Homologous recombination process between foreign gene of interest and the genome of the recepeint cell.

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