A large and reliable DNA codeword library is the key to the success of DNA based computing. Searching for the set of reliable DNA codewords is an NP-hard problem, which can take days on the state-of-art high performance cluster computers. This work presents a hybrid architecture that consists of a general purpose microprocessor and a hardware accelerator for accelerating the discovery of DNA reverse complement, edit distance codes. Two applications of this architecture were implemented and evaluated, including a code generator that uses a genetic algorithm (GA) to produce nearly locally optimal codes in a few minutes, and a code extender that uses exhaustive search to produce locally optimum codes in about 1.5 hours for the case of length 16 codes. The experimental results demonstrate that the GA can find ~99% of the words in locally optimum libraries, and that the hybrid architecture provides more than 1000X speed-up compared to a software only implementation.