Years ago it was a commercial
waterway so it is possible.
We know the river well from Tybee Island to Clyo. As for depth
I would only do it with a scout boat
and/or someone with local knowledge. The lower part of the river (Houlihans to Rincon) runs both directions due to our 8-10 ft tides and that puts the sand bars in some strange places.
Bridges are another concern, when we were running that part of the river (wakeboarding in the wildlife refuge) we didn't have to worry about it as we were in a smaller powerboat and the wake tower could be dropped. There is a bridge just north of the ports
at Houlihan landing and a train tressel that parallels I-95, both are opening bridges but are not staffed. I have no idea the cost or method to have them opened. North of Clyo I am not sure of bridges but since barges used to transit the entire river I would assume all are opening.
The wildlife refure is amazing country, sounds like an adventure, no swimming at night, and good luck.