TY - CHAP
T1 - The Causes for Genomic Instability and How to Try and Reduce Them Through Rational Design of Synthetic DNA
AU - Arbel-Groissman, Matan
AU - Menuhin-Gruman, Itamar
AU - Yehezkeli, Hader
AU - Naki, Doron
AU - Bergman, Shaked
AU - Udi, Yarin
AU - Tuller, Tamir
N1 - Publisher Copyright:
© The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature 2024.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Computational models
KW - DNA damage repair
KW - DNA optimization
KW - Evolvability
KW - Genetic stability
UR - http://www.scopus.com/inward/record.url?scp=85187788666&partnerID=8YFLogxK
U2 - 10.1007/978-1-0716-3658-9_21
DO - 10.1007/978-1-0716-3658-9_21
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C2 - 38468099
AN - SCOPUS:85187788666
T3 - Methods in Molecular Biology
SP - 371
EP - 392
BT - Methods in Molecular Biology
PB - Humana Press Inc.
ER -