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Assume a manuscript written in AmE (if it matters, also assume an American MC).

It would be relatively easy to change spelling, word choice, etc. to make a BrE manuscript. However, since I write with an AmE brain, I feel that such a change would be somewhat lacking (not to mention, I might miss something).

How bad a tactic would it be to send a manuscript in AmE to a British literary agent - keeping in mind the MC is American anyway?

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The best approach is to query the agent first and ask them what their preference is. It is unlikely that they all have the same policy. Asking them first shows them that you are aware of the issue and willing to adjust if required. That shows professionalism, which counts for a lot with agents.

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