The solution I remember from the last time I dealt with Python on .NET (which was admittedly a long time ago) was the opposite - you did use the reified generic

The solution I remember from the last time I dealt with Python on .NET (which was admittedly a long time ago) was the opposite - you did use the reified generics, and there were facilities to create an instance of GenericClass<TWhatever> from within Python. There's a whole dynamic language runtime that is purpose-built for smoothing over a lot of that stuff. What wouldn't work would be to, e.g., create a Python-native list and try to pass it into a function that expects a .NET IList<T>. Which doesn't feel that odd to me - they may have the same name, but otherwise they're very different types that have very different interfaces. That said, the Iron languages never took off. My personal story there is that all the new dynamic features that C# got with the release of the DLR pretty much killed my desire to interact with C# from a dynamic language. The release that gave me Python on .NET also turned C# itself into an acceptable enough Python for my needs.