Therapeutics

TierraBlog-004_Antibody-DrugConjugates.pdf

Liu K, Li M, Li Y, et al. A review of the clinical efficacy of FDA-approved antibody‒drug conjugates in human cancers. Molecular Cancer. 2024;23(1):62. doi:10.1186/s12943-024-01963-7

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Fu Z, Li S, Han S, Shi C, Zhang Y. Antibody drug conjugate: the “biological missile” for targeted cancer therapy. Sig Transduct Target Ther. 2022;7(1):1-25. doi:10.1038/s41392-022-00947-7

Birrer MJ, Moore KN, Betella I, Bates RC. Antibody-Drug Conjugate-Based Therapeutics: State of the Science. JNCI: Journal of the National Cancer Institute. 2019;111(6):538-549. doi:10.1093/jnci/djz035

Chalouni C, Doll S. Fate of Antibody-Drug Conjugates in Cancer Cells. Journal of Experimental & Clinical Cancer Research. 2018;37(1):20. doi:10.1186/s13046-017-0667-1

Balamkundu S, Liu CF. Lysosomal-Cleavable Peptide Linkers in Antibody–Drug Conjugates. Biomedicines. 2023;11(11):3080. doi:10.3390/biomedicines11113080

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Tsuchikama K, Anami Y, Ha SYY, Yamazaki CM. Exploring the next generation of antibody–drug conjugates. Nat Rev Clin Oncol. 2024;21(3):203-223. doi:10.1038/s41571-023-00850-2

Khera E, Dong S, Huang H, de Bever L, van Delft FL, Thurber GM. Cellular-Resolution Imaging of Bystander Payload Tissue Penetration from Antibody-Drug Conjugates. Mol Cancer Ther. 2022;21(2):310-321. doi:10.1158/1535-7163.MCT-21-0580

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Groff D, Carlos NA, Chen R, et al. Development of an E. coli strain for cell‐free ADC manufacturing. Biotechnol Bioeng. 2022;119(1):162-175. doi:10.1002/bit.27961

Antibody-drug conjugates (ADCs) leverage monoclonal antibodies (mAbs) and the potency of anti-cancer compounds to deliver cytotoxic drugs to tumor cells.

Developing effective ADCs involves overcoming challenges in specificity, internalization, stability, and manufacturing to ensure therapeutic efficacy.

Cell-free protein synthesis (CFPS) offers solutions to discover and develop a new wave of ADCs.

Antibody-drug conjugates: A new era in targeted cancer therapy

Cell-Free Protein Synthesis

TierraBlog-003-Cell-FreeSynthesis.pdf

Khambhati K, Bhattacharjee G, Gohil N, Braddick D, Kulkarni V, Singh V. Exploring the Potential of Cell-Free Protein Synthesis for Extending the Abilities of Biological Systems. Front Bioeng Biotechnol. 2019;7. doi:10.3389/fbioe.2019.00248

Irastortza-Olaziregi M, Amster-Choder O. Coupled Transcription-Translation in Prokaryotes: An Old Couple With New Surprises.Front Microbiol. 2020;11:624830.doi:10.3389/fmicb.2020.624830

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Nirenberg MW, Matthaei JH. The dependence of cell-free protein synthesis in E. coli upon naturally occurring or synthetic polyribonucleotides. Proc Natl Acad Sci U S A. 1961;47(10):1588-1602. doi:10.1073/pnas.47.10.1588

Hunt AC, Vögeli B, Hassan AO, et al. A rapid cell-free expression and screening platform for antibody discovery. Nat Commun. 2023;14(1):3897. doi:10.1038/s41467-023-38965-w

Ramm F, Kaser D, König I, et al. Synthesis of biologically active Shiga toxins in cell-free systems. Sci Rep. 2024;14(1):6043.doi:10.1038/s41598-024-56190-3

 Failmezger J, Scholz S, Blombach B, Siemann-Herzberg M. Cell-Free Protein Synthesis From Fast-Growing Vibrio natriegens. Front Microbiol. 2018;9. doi:10.3389/fmicb.2018.01146

Wiegand DJ, Lee HH, Ostrov N, Church GM. Cell-free Protein Expression Using the Rapidly Growing Bacterium Vibrio natriegens. JoVE (Journal of Visualized Experiments). 2019;(145):e59495. doi:10.3791/59495

Ji X, Liu WQ, Li J. Recent advances in applying cell-free systems for high-value and complex natural product biosynthesis. Current Opinion in Microbiology. 2022;67:102142. doi:10.1016/j.mib.2022.102142

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Li J, Zhang L, Liu W. Cell-free synthetic biology for in vitro biosynthesis of pharmaceutical natural products. Synth Syst Biotechnol. 2018;3(2):83-89. doi:10.1016/j.synbio.2018.02.002

SUN ZZ, Robertson DE, TREGO KS, CHIAO AC, IV LEM. Anaerobic cell-free systems and environments and methods for making and using same. Published online August 26, 2020. Accessed May 24, 2024. https://patents.google.com/patent/EP3697803A2/en

Cole SD, Miklos AE, Chiao AC, Sun ZZ, Lux MW. Methodologies for preparation of prokaryotic extracts for cell-free expression systems. Synthetic and Systems Biotechnology. 2020;5(4):252-267. doi:10.1016/j.synbio.2020.07.006

Macek B, Forchhammer K, Hardouin J, Weber-Ban E, Grangeasse C, Mijakovic I. Protein post-translational modifications in bacteria.Nat Rev Microbiol. 2019;17(11):651-664. doi:10.1038/s41579-019-0243-0

Ezure T, Nanatani K, Sato Y, et al. A Cell-Free Translocation System Using Extracts of Cultured Insect Cells to Yield Functional Membrane Proteins. PLOS ONE. 2014;9(12):e112874. doi:10.1371/journal.pone.0112874

Quast RB, Kortt O, Henkel J, et al. Automated production of functional membrane proteins using eukaryotic cell-free translation systems. Journal of Biotechnology. 2015;203:45-53. doi:10.1016/j.jbiotec.2015.03.015

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Marcu K, Dudock B. Characterization of a highly efficient protein synthesizing system derived from commercial wheat germ. Nucleic Acids Res. 1974;1(11):1385-1397. doi:10.1093/nar/1.11.1385

Goshima N, Kawamura Y, Fukumoto A, et al. Human protein factory for converting the transcriptome into an in vitro-expressed proteome,. Nat Methods. 2008;5(12):1011-1017. doi:10.1038/nmeth.1273

Arumugam TU, Ito D, Takashima E, et al. Application of wheat germ cell-free protein expression system for novel malaria vaccine candidate discovery. Expert Rev Vaccines. 2014;13(1):75-85. doi:10.1586/14760584.2014.861747

Buntru M, Vogel S, Spiegel H, Schillberg S. Tobacco BY-2 cell-free lysate: an alternative and highly-productive plant-based in vitro translation system. BMC Biotechnology. 2014;14(1):37. doi:10.1186/1472-6750-14-37

Mikami S, Kobayashi T, Masutani M, Yokoyama S, Imataka H. A human cell-derived in vitro coupled transcription/translation system optimized for production of recombinant proteins. Protein Expr Purif. 2008;62(2):190-198. doi:10.1016/j.pep.2008.09.002

Rosenblum G, Cooperman BS. Engine out of the Chassis: Cell-Free Protein Synthesis and its Uses. FEBS Lett. 2014;588(2):261-268. doi:10.1016/j.febslet.2013.10.016

Mureev S, Kovtun O, Nguyen UTT, Alexandrov K. Species-independent translational leaders facilitate cell-free expression. Nat Biotechnol. 2009;27(8):747-752. doi:10.1038/nbt.1556

Shinoda T, Shinya N, Ito K, et al. Cell-free methods to produce structurally intact mammalian membrane proteins. Sci Rep. 2016;6(1):30442. doi:10.1038/srep30442

Salehi ASM, Smith MT, Bennett AM, Williams JB, Pitt WG, Bundy BC. Cell-free protein synthesis of a cytotoxic cancer therapeutic: Onconase production and a just-add-water cell-free system. Biotechnol J. 2016;11(2):274-281. doi:10.1002/biot.201500237

Porche KB, Lanclos CE, Kwon YC. Challenging Post-translational Modifications in the Cell-free Protein Synthesis System. Synthetic Biology and Engineering. 2023;1(2):10011. doi:10.35534/sbe.2023.10011

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Gupta MD, Flaskamp Y, Roentgen R, et al. Scaling eukaryotic cell-free protein synthesis achieved with the versatile and highyielding tobacco BY-2 cell lysate. Biotechnology and Bioengineering. 2023;120(10):2890-2906. doi:10.1002/bit.28461

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Prokaryotic and eukaryotic systems have unique advantages and disadvantages for CFPS protocols. Prokaryotes are cost-effective with high growth rates, but eukaryotic systems can perform post-translational modifications despite their higher cost.

Successful CFPS requires understanding protein types and factors affecting yields. Different proteins require specific reagents and conditions to optimize transcription efficiency and maximize protein yields.

Advances in strain engineering, such as using engineered strains of E. coli, enhance the production of biologics through CFPS.

Selecting a Cell-Free Protein Synthesis System

TierraBlog-002_BreakingBoundsOfBiology.pdf

Gupta V, Sengupta M, Prakash J, Tripathy BC. Production of Recombinant Pharmaceutical Proteins. Basic and Applied Aspects of Biotechnology. Published online October 23, 2016:77-101. doi:10.1007/978-981-10-0875-7_4

Gregorio NE, Levine MZ, Oza JP. A User’s Guide to Cell-Free Protein Synthesis. Methods Protoc. 2019;2(1):24. doi:10.3390/mps2010024

Zhang L, Lin X, Wang T, Guo W, Lu Y. Development and comparison of cell-free protein synthesis systems derived from typical bacterial chassis. Bioresources and Bioprocessing. 2021;8(1):58. doi:10.1186/s40643-021-00413-2

Schoborg JA, Hodgman CE, Anderson MJ, Jewett MC. Substrate replenishment and byproduct removal improve yeast cell-free protein synthesis. Biotechnol J. 2014;9(5):630-640. doi:10.1002/biot.201300383

Garamella J, Marshall R, Rustad M, Noireaux V. The All E. coli TX-TL Toolbox 2.0: A Platform for Cell-Free Synthetic Biology. ACS Synth Biol. 2016;5(4):344-355. doi:10.1021/acssynbio.5b00296

Yim SS, Johns NI, Noireaux V, Wang HH. Protecting Linear DNA Templates in Cell-Free Expression Systems from Diverse Bacteria. ACS Synth Biol. 2020;9(10):2851-2855. doi:10.1021/acssynbio.0c00277

Carlson ED, Gan R, Hodgman CE, Jewett MC. Cell-Free Protein Synthesis: Applications Come of Age. Biotechnol Adv. 2012;30(5):1185-1194. doi:10.1016/j.biotechadv.2011.09.016

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Jin X, Kightlinger W, Kwon YC, Hong SH. Rapid production and characterization of antimicrobial colicins using Escherichia coli-based cell-free protein synthesis. Synthetic Biology. 2018;3(1):ysy004. doi:10.1093/synbio/ysy004

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Dondapati, S.K., Stech, M., Zemella, A. et al. Cell-Free Protein Synthesis: A Promising Option for Future Drug Development. BioDrugs 34, 327–348 (2020). https://doi.org/10.1007/s40259-020-00417-y

Proteins are vital for advancing an array of biotechnological applications, including drug development.

Traditional cell-based synthesis methods face challenges with scalability, high costs, and restrictions on producing complex proteins.

Cell-free protein synthesis (CFPS) overcomes these limitations by enabling efficient protein production without cellular constraints.

The Tierra Protein Platform utilizes AI and automation to rapidly synthesize a diverse range of proteins, enhancing research and development efforts.

Breaking the bounds of biology: innovations in cell-free protein synthesis

TierraBlog-001_FromTargetstoTreatment.pdf

Evolving strategies and application of proteins and peptide therapeutics in cancer treatment. Biomed. Pharmacother. 163, 114832 (2023).

Seebacher, N. A., Stacy, A. E., Porter, G. M. & Merlot, A. M. Clinical development of targeted and immune based anti-cancer therapies. J. Exp. Clin. Cancer Res. 38, 1–39 (2019).

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Dondapati, S. K., Stech, M., Zemella, A. & Kubick, S. Cell-Free Protein Synthesis: A Promising Option for Future Drug Development. BioDrugs 34, 327–348 (2020).

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The cancer proteome, with its remarkable diversity, encompasses a vast array of proteins distinguished by their functions and cellular locations, underscoring the multifaceted nature of cancer biology.

Targeted protein-based therapies, particularly those centered around antibodies, are on the rise, yet they encounter significant hurdles in terms of developability and manufacturability.

Pioneering advancements in gene expression and protein engineering are catalyzing a revolution in the generation of personalized and more efficacious protein-based cancer treatments.

From targets to treatments: insights from the cancer proteome

Experience AI-driven custom protein synthesis at scale, only from Tierra.

Discover the world of protein-powered cell-free research.