RNAi has been discovered to have unbelievable potential to manage and treat cancer, by silencing genes through short interfering, double-stranded RNA fragments called siRNAs. This has led
to the development of a technology that allows for siRNA drug delivery into the entire population of cells, both primary and tumor-causing, without being toxic to the cells. However, the size and negative electrical charge of the siRNA, prohibits them from readily entering the cell. This problem was overcome by utilizing a small section of protein called a peptide transduction domain (PTD), which has the ability to permeate cell membranes, as a delivery mechanism. However, simply adding the siRNAs to a PTD didn't work due to siRNAs having a highly negative charge and PTDs having a positive charge, which results in aggregation with no cellular delivery. This issue was overcome by making a PTD fusion protein with a double-stranded RNA-binding domain, termed PTD-DRBD, which masks the siRNA's negative charge. This allows the resultant fusion protein to enter the cell and deliver the siRNA into the cytoplasm where it specifically targets mRNAs from cancer-promoting genes and silences them.
It was found that the entire cellular population undergoes a maximum RNAi response. Also, no toxicity to the cells or innate immune responses, and a minimal number of transcriptional off-target changes occur. These RNAi methods can be continually tweaked to combat new mutations – a way to overcome a major problem associated with current cancer therapies.
Posted by: 42034377
Reference: Science daily (2009). Future of Personalized Cancer Treatment: New System Delivers RNA into Cells. Viewed: May 20, 2009, at http://www.sciencedaily.com/releases/2009/05/090517081157.htm
to the development of a technology that allows for siRNA drug delivery into the entire population of cells, both primary and tumor-causing, without being toxic to the cells. However, the size and negative electrical charge of the siRNA, prohibits them from readily entering the cell. This problem was overcome by utilizing a small section of protein called a peptide transduction domain (PTD), which has the ability to permeate cell membranes, as a delivery mechanism. However, simply adding the siRNAs to a PTD didn't work due to siRNAs having a highly negative charge and PTDs having a positive charge, which results in aggregation with no cellular delivery. This issue was overcome by making a PTD fusion protein with a double-stranded RNA-binding domain, termed PTD-DRBD, which masks the siRNA's negative charge. This allows the resultant fusion protein to enter the cell and deliver the siRNA into the cytoplasm where it specifically targets mRNAs from cancer-promoting genes and silences them.It was found that the entire cellular population undergoes a maximum RNAi response. Also, no toxicity to the cells or innate immune responses, and a minimal number of transcriptional off-target changes occur. These RNAi methods can be continually tweaked to combat new mutations – a way to overcome a major problem associated with current cancer therapies.
Posted by: 42034377
Reference: Science daily (2009). Future of Personalized Cancer Treatment: New System Delivers RNA into Cells. Viewed: May 20, 2009, at http://www.sciencedaily.com/releases/2009/05/090517081157.htm

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