The incident was first reported shortly after 5 a.m. as a Chevy Bolt that slammed into the center divider on the northbound side of the freeway near the Burbank Boulevard off-ramp.
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Officers and paramedics arrived to find a driver with a gunshot wound. The man was rushed to a hospital in unknown condition.
No suspect information was available and they remain on the loose. Police say road rage is a possible factor in the shooting.
"If someone cuts you off, they don't use their blinkers, whatever it is, speeding, back up, withdraw from the situation. If the person is still following you, you believe that they are a danger to you, please call 911 and head to your closest police station," said CHP Officer Casey Ramstead.
Early morning traffic was backed up on the northbound side of the freeway as authorities conducted an investigation at the scene. Two northbound lanes were open for several hours while three others remained closed.
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Shortly after 8 a.m., CHP shut down all northbound lanes again as officers scoured the area for evidence. Lanes reopened around 12 p.m.
Editorial note: An earlier version of this story stated the incident happened in Van Nuys, but the location is in the neighboring Sherman Oaks neighborhood.