For gene therapy applications, retroviral vectors must be purified and concentrated by ultracentrifugation, a process that tends to strip off surface proteins needed for cell infectivity. In this issue, Powell et al. use DNA shuffling to evolve variants of the type C Moloney murine leukemia virus (MLV) retrovirus—the parent for most retroviral gene transfer vectors—with enhanced resistance to envelope breakdown during ultracentrifugation. They shuffled the envelope genes from six murine retroviruses, put them back into a retrovirus backbone, and reassembled viral particles by transfecting cells with the recombinant viral library. The retroviruses were subjected to several rounds of ultracentrifugation and selection, and a number of variants were identified with heightened resistance. Stress resistance of this kind is difficult to engineer by rational design, so the success of DNA shuffling to improve this property suggests that the technology could be harnessed to overcome previously intractable limitations of viral gene therapy vectors (see pp. 1244 and 1279).