The crash happened in the southbound lanes around 8:20 a.m. Wednesday.
Video from Chopper 6 showed the tractor-trailer and three heavily damaged passenger vehicles at the scene.
According to police, the tractor-trailer struck the rear of a Jeep. That Jeep then hit a Subaru, which overturned and struck a Toyota.
Multi-vehicle crash on I-295
The driver of the Subaru was taken to the hospital with serious injuries. The drivers of the Jeep and Toyota suffered non-life-threatening injuries.
The southbound lanes were shut down for several hours. All lanes were reopened by 3 p.m.
There was no word on any charges related to this crash.
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