Oncogenes are suppressed in normal cells, thus, using interference RNAs should not affect normal cells and should suppress cancer cell growth.
Yes, they can. Comparing to chemical inhibitors, they might be more specific (although, siRNAs also have off-target effects) but less potent. Also, you rarely get a tumor that only depends on one oncogene. Cancer can be initiated by one oncogene but tumor cells rapidly accumulate mutations and activate several oncogenic pathways, so you would need to treat with variou siRNAs against quite a few oncogenes that you would know that are important for the survival/growth of these cells. In any case there are a lot of studies trying to deliver siRNAs spcifically to tumor cells with nanoparticles (for a review see first link). On the other hand there is at least one study for using RNA interference against tumor angiogenesis (second link).
http://www.ncbi.nlm.nih.gov/pubmed/24724498
http://www.ncbi.nlm.nih.gov/pubmed/23358650
Yes, they can. Comparing to chemical inhibitors, they might be more specific (although, siRNAs also have off-target effects) but less potent. Also, you rarely get a tumor that only depends on one oncogene. Cancer can be initiated by one oncogene but tumor cells rapidly accumulate mutations and activate several oncogenic pathways, so you would need to treat with variou siRNAs against quite a few oncogenes that you would know that are important for the survival/growth of these cells. In any case there are a lot of studies trying to deliver siRNAs spcifically to tumor cells with nanoparticles (for a review see first link). On the other hand there is at least one study for using RNA interference against tumor angiogenesis (second link).
http://www.ncbi.nlm.nih.gov/pubmed/24724498
http://www.ncbi.nlm.nih.gov/pubmed/23358650
The answer is yes but how. RNAi does not automatically go everywhere. The source of RNAi (like siRNA or shRNA or miRNA) cannot be put (transfect) into cells easily. Transfection is not a easy process especially in vivo. So, the question is how to do that effectively.
thank you, we probably can eat the RNAi (e.g. rice), if they can make the RNAi as pills.? Attached is RNAi consumption by human.
we, only, have to understand why did the MIR 168a "survive" the journey from rice to target cells, i.e. the liver cells using microvesicles mv. Apply the principles to a "designed" mir RNA and or si RNA.(?)
This could be applied to many diseases such as: cancer: inhibiting cancer active onco genes, and may be inhibiting the "invading immune cells produce cytokines" which attacks the beta pancreatic cells in diabetics.?
http://www.nature.com/cr/journal/v22/n1/full/cr2011158a.html
we, only, have to understand why did the MIR 168a "survive" the journey from rice to target cells, i.e. the liver cells using microvesicles mv. Apply the principles to a "designed" mir RNA and or si RNA.(?)
As cancer is not induced by activity of one oncogene and at least 5-7 genes are involved in cancer, using siRNA against one of them will probably not enough for cancer suppression. But in some instances we can make the cells less malignant by using siRNA
thank you, if we can designed for one of the onco gene we probably can design for the rest for them.?
Yes, provided you know what RNA products you want to interfere with!
It is possible to evaluate the RNA products which we want to interfere with. On other hand, siRNA can also aid in "heterochromatine spreading" which, I think, would be more effective in silencing onco genes.? However, I am not sure if siRNA can be delivered orally as in the study above i.e. rice, MIR168a.(?)
How many oncogenes you wanted to deal with in one cancer type? How many mutated genes are there? In case of virally-induced cancer (such as HPV vs cervical cancer) we know it is E6 and E7. If these are silenced then the whole story is done. Now the question is; what is the success rate of delivering these siRNA-E6/E7 into human? Answer, it is very low. The reason beyond this is actually the delivery itself and the fact the off-target effect is a very challenging issue in siRNA silencing. Also, if you succeed and deliver it then we come to another issue that is immune stimulation.
Therefore, in many studies, they use siRNA to screen then may be shortcut the whole process by using small molecule inhibitors, which can cease the protein action rather than the mRNA. Yes, it has some unspecific response rate but at least we know it can go far in the clinical trials than siRNA.
Hopefully this helps :)
thank you, the microvesicles in the study attached seems to work well delivering the micrRNA 168a to the "target" liver cells. Can we use genetic engineered rice with, lets say, siRNA-E6/E7 encoded in the rice to be taken up by microvesicles. This microvesicles could, potentially, deliver the siRNA-E6/E7 to target cancer cells.?
http://www.nature.com/cr/journal/v22/n1/full/cr2011158a.html
Yes siRNAs can be used to suppress oncogene expression. Here is a recent paper that demonstrates this against Kras. http://www.ncbi.nlm.nih.gov/pubmed/25281617
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