Alpha1 Record ID: 44A644BC
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Robinson, N. E.; Paul, J.-S.; Zhang, W.; Zhang, H.; Wang, S.; Zhao, T.; Abraham, E.; Simpson, B.; Wang, K.
Reliable and cost effective de novo DNA production has become central to studying and engineering biology. Short synthetic single-stranded DNA oligo pools offer substantially reduced costs at the sacrifice of yield and individual oligo isolation. Efficiently constructing longer synthetic double-stranded DNA molecules from oligo pools as the input has remained an engineering challenge with the potential to drastically reduce costs, labor, and experimental turn-around time. Here we show one-pot, parallel assembly of hundreds of DNA fragments simultaneously into dozens of defined constructs with high fidelity using Sidewinder. We designed a novel string-based bespoke barcode design algorithm which rapidly generates Sidewinder barcodes at unprecedented scale. We apply the new algorithm to Sidewinder using oligo pools, demonstrating construct-specific amplification from pooled assemblies with misconnection rates as low as 1 in 10,000,000. Further, we demonstrate universal amplification of pooled assemblies to generate a library of specific target sequences that we combine with in vitro hierarchical assembly to 12.5 kilobases.
DNA synthesis goes mega-scale with Sidewinder tech turning oligo pools into complex constructs in one glorious pot like a molecular assembly line on steroids, supercharging AI-driven synthetic biology dreams with parallel wizardry.
Highlighted by Adrian Woolfson (@AdrianWoolfson) for its scalability potential in synthetic bio, sparking interest among biotech and AI-biology folks with solid likes and shares
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CD4⁺ T cells confer transplantable rejuvenation via Rivers of telomeres
Lanna, A.; Valvo, S.; Dustin, M.; Rinaldi, F.
Using a GPT-5-driven autonomous lab to optimize the cost and titer of cell-free protein synthesis
Smith, A. A.; Wong, E. L.; Donovan, R. C.; Chapman, B. A.; Harry, R.; Tirandazi, P.; Kanigowska, P.; Gendreau, E. A.; Dahl, R. H.; Jastrzebski, M.; Cortez, J. E.; Bremner, C. J.; Hemuda, J. C. M.; Dooner, J.; Graves, I.; Karandikar, R.; Lionetti, C.; Christopher, K.; Consiglio, A. L.; Tran, A.; McCusker, W.; Nguyen, D. X.; Nunes da Silva, I. B.; Bautista-Ayala, A. R.; McNerney, M. P.; Atkins, S.; McDuffie, M.; Serber, W.; Barber, B. P.; Thanongsinh, T.; Nesson, A.; Lama, B.; Nichols, B.; LaFrance, C.; Nyima, T.; Byrn, A.; Thornhill, R.; Cai, B.; Ayala-Valdez, L.; Wong, A.; Che, A. J.; Thavaraj
A Single-Cell and Spatial 3D Multi-omic Atlas of Developing Human Basal Ganglia and Inhibitory Neurons
Heffel, M. G.; Xu, H.; Pastor-Alonso, O.; Li, X.; Baig, M. S.; Irfan Ghoor, R.; Li, R.; Kern, C.; Kum, J.; Zhang, Y.; Paino, J.; Tsai, M. J.; Tai, C.-Y.; Tucker, G.; Zhao, Z.; Hou, A.; von Behren, Z.; Bhade, M.; Li, S.; Sandoval, K.; Scholes, J.; Codrea, F.; Calimlim, J.; Liao, E. K.; Leung, G.; Kim, J.; Eskin, E.; Flint, J.; Cotter, J. A.; Pasaniuc, B.; Bintu, B.; Zhu, Q.; Mukamel, E. A.; Ernst, J.; Paredes, M. F.; Luo, C.
Prediction of transformative breakthroughs in biomedical research
Davis, M. T.; Busse, B. L.; Arabi, S.; Meyer, P.; Hoppe, T. A.; Meseroll, R. A.; Hutchins, B. I.; Willis, K. A.; Santangelo, G. M.