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December 29, 2023, San Diego, CA – Scientists have made a groundbreaking stride in the realm of genetic engineering by uncovering the potential of artificial DNA to reshape the synthesis of proteins. The research, spearheaded by the University of California San Diego’s Skaggs School of Pharmacy and Pharmaceutical Sciences, introduces a paradigm shift by expanding the traditional genetic alphabet.
The study, published in Nature Communications, delves into the addition of new nucleotides to the existing four-letter genetic alphabet. Dr. Dong Wang, senior author and professor at UC San Diego, explains the implications, stating, “Expanding the genetic code could greatly diversify the range of molecules we can synthesize in the lab and revolutionize how we approach designer proteins as therapeutics.”
The team, co-led by Dr. Steven A. Benner of the Foundation for Applied Molecular Evolution and Dr. Dmitry Lyumkis of the Salk Institute for Biological Studies, embarked on a journey to examine if synthetic nucleotides could be integrated into the natural DNA framework. Their findings showcase a remarkable discovery: RNA polymerase, a pivotal enzyme in protein synthesis, seamlessly recognizes and transcribes these artificial base pairs akin to natural counterparts.
Dr. Wang elucidates, “Our synthetic base pairs conform to a similar structure as standard base pairs, allowing them to seamlessly integrate into the transcription process.”
This pioneering approach, utilizing the Artificially Expanded Genetic Information System (AEGIS), introduces two new base pairs. Initially conceived under a NASA-supported initiative by Dr. Benner, AEGIS initially aimed to explore the potential development of extraterrestrial life.
The significance of this breakthrough extends beyond synthetic biology; it corroborates the long-standing tautomer hypothesis proposed during the era of Watson and Crick. This hypothesis suggests that the standard four nucleotides possess the capability to form mismatched pairs due to tautomerization, potentially causing genetic mutations in DNA sequences.
Dr. Wang further elaborates, “Our findings offer the first direct structural evidence supporting the tautomer hypothesis, indicating that tautomerization occurs during the transcription process.”
The team’s next phase involves extensive exploration to ascertain the consistency of their observations across various combinations of synthetic base pairs and cellular enzymes. Dr. Wang expresses enthusiasm for assembling a collaborative team aimed at comprehensively understanding the molecular dynamics underlying transcription in an expanded genetic alphabet.
The prospects unveiled by this research are vast, signaling a potential shift in our capacity to engineer custom proteins and develop innovative therapeutics. As Dr. Wang asserts, “There could be many other possibilities for new letters besides what we’ve tested here, but we need to do more work to figure out how far we can take it.”
The world of genetics stands on the cusp of a transformative era, driven by the ingenuity of these scientific pioneers, poised to redefine the boundaries of genetic engineering and protein design.
