Artificial DNA breakthrough leads to development of designer proteins
Scientists have long been captivated by the possibilities of DNA, the molecule that stores the genetic instructions for all living organisms. (CREDIT: Creative Commons)
Scientists have long been captivated by the possibilities of DNA, the molecule that stores the genetic instructions for all living organisms. With its four-letter alphabet – adenine (A), thymine (T), guanine (G), and cytosine (C) – DNA orchestrates the complex processes of life.
However, researchers have envisioned expanding this alphabet to create entirely new genetic codes, unlocking a realm of unprecedented biological potential.
Recently, a collaborative effort among researchers from the University of California San Diego, the Foundation for Applied Molecular Evolution, and the Salk Institute for Biological Studies has made significant strides in this direction.
Overall structures of E. coli RNA polymerase elongation complex harboring unnatural base pair. (CREDITL Nature Communications)
Their breakthrough, published in Nature Communications, introduces a groundbreaking DNA system with six letters instead of the traditional four, offering a glimpse into a future where customized proteins and innovative biological applications could become commonplace.
The concept of expanding the genetic code beyond its natural repertoire is nothing short of revolutionary. Dong Wang, Ph.D., a professor at UC San Diego's Skaggs School of Pharmacy and Pharmaceutical Sciences and the study's senior author, envisions a world where the addition of new "letters" to DNA could unleash a plethora of possibilities.
"Life on Earth is amazingly diverse with just four nucleotides, so imagine what we could do with more," Wang remarked. "By expanding the genetic code, we could create new molecules that have never been seen before and explore new ways of making proteins as therapeutics."
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Central to this breakthrough is the utilization of a synthetic DNA system known as AEGIS – Artificially Expanded Genetic Information System – developed by Steven A. Benner, Ph.D., at the Foundation for Applied Molecular Evolution.
AEGIS introduces two new letters, Z and P, to the DNA alphabet, augmenting the existing adenine-thymine-guanine-cytosine framework.
These synthetic nucleotides seamlessly integrate into the DNA helix, mimicking the shape and size of natural nucleotides. Remarkably, enzymes responsible for DNA replication and transcription, such as RNA polymerase, recognize and process AEGIS DNA akin to natural DNA.
The researchers' ingenious approach involved designing artificial nucleotides that mirror the geometric properties of their natural counterparts. By targeting RNA polymerase, a pivotal enzyme in DNA transcription, they demonstrated the feasibility of incorporating synthetic nucleotides into the genetic code.
Through meticulous experimentation, the team validated the efficacy of AEGIS DNA transcription by bacterial RNA polymerase, highlighting the adaptability and robustness of biological machinery.
"This is a remarkable demonstration of how robust and adaptable the biological machinery is," Wang commented. "By mimicking the natural shape of DNA, our synthetic letters can sneak in and be used to make new proteins."
The implications of this breakthrough extend far beyond the confines of laboratory experimentation. The ability to engineer proteins with tailored functionalities holds immense promise for diverse applications, including targeted cancer therapy and sustainable biofuel production.
However, significant challenges lie ahead. Optimizing the integration of new nucleotides into the genetic code, ensuring their stability within the genome, and fully exploring the potential of this expanded code demand further investigation.
Nonetheless, this milestone marks a profound leap forward in our comprehension of life's fundamental blueprint. It heralds the dawn of a new era in biological design, where the boundaries of possibility are constrained only by the limits of imagination.
"These new proteins could have applications in medicine, biotechnology, and bioengineering," Wang affirmed. "We are only scratching the surface of what we can do with artificial DNA."
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