Disclosed herein are targeted chimeric polypeptides, compositions thereof, expression vectors, and methods of use thereof, for the generation of transgenic cells, tissues, plants, and animals. The compositions, vectors, and methods of the present invention are also useful in gene therapy and cell therapy techniques. The chimeric polypeptide includes a CRISPR-Cas domain and a recombinase domain.

The present disclosure provides systems and methods for increasing production of an alkaloid product through the epimerization of a (S)-1-benzylisoquinoline alkaloid to a (R)-1-benyzlisoquinoline alkaloid via an engineered epimerase in an engineered host cell. A (S)-1-benzylisoquinoline alkaloid is contacted with said engineered epimerase. Contacting said (S)-1-benzylisoquinoline alkaloid with said engineered epimerase converts said (S)-1-benzylisoquinoline alkaloid to said (R)-1-benzylisoquinoline alkaloid.

Disclosed are replication-enhanced oncolytic adenoviruses. These oncolytic adenoviruses have tumor-specific replication capable of enhanced tumor oncolysis and enhanced therapeutic transgene expression. Also disclosed are methods comprising administering a replication-enhanced oncolytic adenovirus for patients suffering from a cancer.