Lots of good information already provided, so I'll just ad a tidbit more:
1. As stated, unless your 5.3L can run E85 from the factory, you won't see much of an improvement because it's not a high compression motor like the 6.2L. But, you may feel a difference just because of the way E85 burns in the engine.
2. I've been running it in my 2008 6.2L now at a blend of appropriately 30% of total fuel used (if the computer says inused 21 gallons, then 7 of E85 get put in first). Then top the tank with 87. This has proven to be a fun, economical (both cost per mile, and smiles per gallon) way to wake up this animal.
3. The cleaning characteristics are fantastic, and as
@swathdiver stated, it takes a few tanks for the ECM to acclimate to it.
So, overall, it won't hurt your vehicle. If you don't have the flex fuel designated engine/PCM then I would experiment with some blend ratios and see what feels good to you and math's out to your liking. I've found a sweet spot for the driving I do with my blend - and some slight tuning of the spark tables and trans shift points.