Possibly. But which direction would you go?
You could move back in time - that would allow Wash and Shepherd back but eliminiate Simon and River. Or could move forward but that still eliminates Simon and River as it is unlikely they would remain onboard a smuggler's ship without the need to run/hide. (They could, but the plot device would be a stretch).
You could build basically a spinoff based on Mal and Zoe, but I'm not sure it could retain the charm the original series had.
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