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Dodece said:
@twestern remember to get that red syringe from the little sister before you go fight the boss. Listen to your final radio message if your confused. That is a very easy thing to miss if you get in a rush. However without it you cannot fight the final boss. So logically the game should freeze up.

I have played through the game twice so obviously I have a vastly different take. I suppose I will have to create my own thread since I also want to share spoiler material.

 I don't think you can even get to the final boss without the syrings even if that was the case.  My game was also freezing a good ways before that (about an hour) and it was something to do with my cache.  After holding the LB and RB buttons immediatly after starting the game and letting go after the 2K logo fades to black it worked.