How AstraZeneca created an automated DNA assembly framework to support rapid and cost-efficient construct generation

Introduction

It takes around 10 years and millions to sometimes billions of dollars for most new drugs to make it to market. Unsurprisingly, this timeline and cost profile doesn’t cut it for drug development patients, companies, and clinical trial sponsors. One of the earliest steps that can be optimized  is DNA construct development for early drug discovery, as it affects  all downstream processes.

An essential first step in drug discovery is recombinant protein production. Expression and purification of the intended target protein enables candidate drug screening as well as structural and mechanistic interrogations that guide the design and evaluation of candidate drugs. Later, cell lines are engineered and used in in vitro screening to evaluate toxicity and confirm a candidate drug’s mode of action. These early tests are critical for eliminating ineffective and toxic drugs early, before billions of dollars are spent on clinical trials doomed to fail.

DNA constructs — artificially designed vectors or plasmids that deliver target DNA sequences into cells, where the gene product is produced — underpin recombinant protein production and cell line engineering. Rapid and flexible generation of these constructs at scale is one of the most limiting first steps in drug discovery. A large time sink associated with this process is the de novo synthesis of long coding sequences, a challenge that modular cloning kits haven’t been able to solve effectively. 

To address this, AstraZeneca developed a comprehensive DNA assembly framework, which they integrated into Benchling to support rapid, cost-efficient, and scalable construct generation. Their unique solution takes an unheard-of 3 weeks and led to cost savings from 50 to 90%.