I am performing an siRNA knockdown in post mitotic neurons, I know the effects will last a week, but I want to try up to 3 weeks. Any help appreciated :)
with shRNA effects are prolonged, but with regular synthetic siRNA transfection knockdown is max at day 1-2 then at day 3-4 its less, and a week later its minimal (depends on cells, misc conditions etc). you can re-transfect cells every 3-5 days using RNAiMax or other good reagent. if conditions are carefully optimized and you are not loading cells with excess of lipid - there is minimal to no toxicity. we've done it many times- for 2-3 week long in vitro studies, using Silencer Select and other siRNAs
This link may be useful in this case: https://www.thermofisher.com/pl/en/home/references/ambion-tech-support/rnai-sirna/tech-notes/duration-of-sirna-induced-silencing.html
Depending on the siRNA you use and a company that provides it, you may expect different timecourse of silencing - in the one that I linked for you, 5 days seems to be still a very high silencing, but then silencing lessens. If you want silence genes for longer times, try transfecting neurons with a plasmid encoding shRNA, for example, pSuper, or pSuperior https://www.addgene.org/vector-database/4233/ , https://www.addgene.org/vector-database/4240/