Directed evolution in human cells via adenoviral replication

The discovery and optimization of biomolecules that reliably function in metazoan cells is imperative for both basic biological research, and therapeutic development. Typically, researchers turn to directed evolution either in vitro, in bacteria, or in yeast, to mutate, select, and amplify biomolecules of interest (BOls) with new and highly-tailored activities. Unfortunately, BOIs evolved in these environments often fail to function when translated into the complex environment of metazoan cells. Unique metazoan biology such as sophisticated proteostasis networks, complex cell signaling pathways, distinctive post-translational modifications, cellular trafficking, and highly regulated chromatin architecture can all derail the activity of BOIs evolved in simpler systems. Current approaches to directed evolution in metazoan cells rely on labor-intensive and time-consuming screening approaches that have a high potential for false positives.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Chemistry

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2019

Author dc:creator

• Berman, Chet Michael.

Advisor dc:contributor.advisor

• Matthew D. Shoulders.

• Chemistry.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/121778

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/121778