You can do it with $

(me/rewrite '[:A
              [:B [:C 1 2] [:C 3 [:D 4 5]]]
              [:B [:C 6 7] [:C 8 [:D 9 10]]]]
  (me/$ ?loc [:D 4 5 :as ?D])
  (me/$ ?loc [:D YOU WIN]))
;; =>
[:A
 [:B [:C 1 2] [:C 3 [:D YOU WIN]]]
 [:B [:C 6 7] [:C 8 [:D 9 10]]]]

Or like @U5K8NTHEZ said, you can use strategies.

I found out that there is an updating function built in so I went with that in the end.