The Causes for Genomic Instability and How to Try and Reduce Them Through Rational Design of Synthetic DNA.

Abstract

Genetic engineering has revolutionized our ability to manipulate DNA and engineer organisms for various applications. However, this approach can lead to genomic instability, which can result in unwanted effects such as toxicity, mutagenesis, and reduced productivity. To overcome these challenges, smart design of synthetic DNA has emerged as a promising solution. By taking into consideration the intricate relationships between gene expression and cellular metabolism, researchers can design synthetic constructs that minimize metabolic stress on the host cell, reduce mutagenesis, and increase protein yield. In this chapter, we summarize the main challenges of genomic instability in genetic engineering and address the dangers of unknowingly incorporating genomically unstable sequences in synthetic DNA. We also demonstrate the instability of those sequences by the fact that they are selected against conserved sequences in nature. We highlight the benefits of using ESO, a tool for the rational design of DNA for avoiding genetically unstable sequences, and also summarize the main principles and working parameters of the software that allow maximizing its benefits and impact.