Biology:Abbreviation for D2P

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D2P[1]or D to P (an abbreviation for DNA to protein) is the core technology for in vitro protein synthesis, cell-free protein synthesis system.

Introduction

With 20 years of R&D development, Kangma Healthcode has developed the most advanced D2P cell-free protein synthesis system. The D2P system has been developed basing on genome-editing of the yeast Kluyveromyces, which is a commonly used industrial-grade yeast with a fast growth rate and better food and drug safety feature comparing to other yeast express platform.[2] Powered by genetic modification,[1] evolved sequence alogrithm and manufacturing technology, the D2P system has improved in vitro protein expression efficiency by over 100-fold compared to the in vivo yeast strain. It also has completely eliminated non-specific glycosylations, increased chaperone activity with improved protein folding and enzyme activities. The D2P system could be used to translate a gene of interest into the protein with milligram-to-gram yield directly from nanograms of DNA template. The D2P system is an innovative pulse in the protein expression technology, and could bring a significant change for protein production in the fields of R&D and world-wide industrial manufacture.

Technology background

In current market, various cell-free expression systems have existed, each with their own limitations for wide usage. The Escherichia coli (E. coli)based cell-free synthesis could produce high-yield proteins, however most are limited to proteins with the smaller molecule weights or less folding challenge. [3][4]The insect cells or mammalian cells based cell-free synthesis is high cost due to their long, complicated process of cell culture and preparation of cell extraction. In addition, tedious mRNA preparation steps or large scale of DNA templates are required to be translated into the target protein, which make the production of protein takes even longer time. With all those limitation, cell-free protein synthesis had been only used in few laboratories in the past half century since its first evention.[5]

Applications

More protein drugs/biologics, eg. enzyme, antibody et. al. have been manufactured in a continously growing scale worldwide.[6] With better understandings human system, signal pathways and diseases by systems biology, the development and manufacture of protein drugs have become a recognized trending for the global pharmaceutical industry. The large-scale industrial preparation and production of protein drugs are now only made using traditional in vivo cell culture[7] [8] or exaction from living organisms. [9] Both are time consuming (a producing cycle could take weeks to months, or even years) and labour intensive with heavily manual machining of biologics materials. The high cost of traditional cell-based protein synthesis, [10] in certain extent, limits the large-scale production of protein drugs, their medical applications, deprives patients need, and continuously burdens the healthcare budget. [11] Therefore, it is an urgent needs to have a higher yield, lower cost, faster processed protein synthesis system.

References

  1. 1.0 1.1 Guo M, Zhang XL, Wang HP, Wang J, Xu K, Chen QJ, Yu X. "Synthesis system, preparation, kit and preparation method of in-vitro DNA-to-Protein (D2P)". https://patentscope.wipo.int/search/zh/detail.jsf;jsessionid=0198B006BCC71B17DBF4694B3140B426.wapp2nB?docId=CN232266527&_cid=P21-K5IOY4-94254-22. 
  2. https://www.fda.gov/food/food-ingredients-packaging/generally-recognized-safe-gras
  3. Kim HC, Kim TW, Kim DM (2011). "Prolonged production of proteins in a cell-free protein synthesis system using polymeric carbohydrats as an energy source.". Process Biochemistry 46(6): 1366-9. https://www.sciencedirect.com/science/article/abs/pii/S1359511311001048. 
  4. Zawada JF, Yin G, Steiner AR, Yang J, Naresh A, Roy SM, Gold DS, Heinsohn HG, Murray CJ (2011). "Microscale to manufacturing scale-up of cell-free cytokine production--a new approach or shortening protein production development timelines.". Biotechnology and Bioengineering 108: 1570-1578. https://onlinelibrary.wiley.com/doi/full/10.1002/bit.23103. 
  5. Zawada JF, Yin G, Steiner AR, Yang J, Naresh A, Roy SM, Gold DS, Heinsohn HG, Murray CJ (1954). "Relation between phosphate energy donors and incorporation of labeled amino acids into proteins.". J.Biol.Chem. 209: 337-354. http://m.jbc.org/content/209/1/337.long?view=long&pmid=13192089. 
  6. https://www.grandviewresearch.com/press-release/global-biologics-market
  7. Decker EL, Reski R (2008). "Current achievements in the production of complex biopharmaceuticals with moss bioreactors". Bioprocess and Biosystems Engineering 31: 3-9. https://link.springer.com/article/10.1007%2Fs00449-007-0151-y. 
  8. https://weekly.biotechprimer.com/biomanufacturing-how-biologics-are-made/;
  9. https://en.wikipedia.org/wiki/Biopharmaceutical
  10. https://health.usnews.com/health-news/health-wellness/articles/2015/02/06/why-are-biologic-drugs-so-costly
  11. https://www.modernhealthcare.com/providers/rising-prices-drive-estimated-6-medical-cost-inflation-2020