Preferential germline usage and VH/VL pairing observed in human antibodies selected by mRNA display

Protein Engineering, Design & Selection : PEDS
Lei ChenChung-Ming Hsieh

Abstract

Since the invention of phage display, in vitro antibody display technologies have revolutionized the field of antibody discovery. In combination with antibody libraries constructed with sequences of human origin, such technologies enable accelerated therapeutic antibody discovery while bypassing the laborious animal immunization and hybridoma generation processes. Many in vitro display technologies developed since aim to differentiate from phage display by displaying full-length IgG proteins, utilizing eukaryotic translation system and codons, increasing library size or real-time kinetic selection by fluorescent activated cell sorting. We report here the development of an mRNA display technology and an accompanying HCDR3 size spectratyping monitor for human antibody discovery. Importantly, the mRNA display technology maintains a monovalent linkage between the mRNA (genotype) and display binding protein (phenotype), which minimizes avidity effect common in other display systems and allows for a stringent affinity and off-rate selection. The mRNA display technology successfully identified 100 human antibodies in 15 different selections against various targets from naïve human antibody libraries. These antibodies in general have h...Continue Reading

References

Apr 5, 1986·Journal of Molecular Biology·R FreudlU Henning
May 13, 1997·Proceedings of the National Academy of Sciences of the United States of America·J Hanes, A Plückthun
Jun 1, 1997·Nature Biotechnology·E T Boder, K D Wittrup
Nov 14, 1997·Proceedings of the National Academy of Sciences of the United States of America·R W Roberts, J W Szostak
Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·C RaderC F Barbas
Jul 13, 2000·Methods in Enzymology·R LiuR W Roberts
Oct 29, 2000·Advances in Protein Chemistry·A PlückthunL Jermutus
Mar 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·D S WilsonJ W Szostak
Sep 3, 2002·Chemistry & Biology·Lihui XuDasa Lipovsek
Dec 25, 2002·Journal of Molecular Biology·Stefan EwertAndreas Plückthun
Mar 14, 2003·Trends in Biochemical Sciences·Terry T TakahashiRichard W Roberts
Feb 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Richard OdegripDuncan McGregor
Jun 28, 2005·Protein Engineering, Design & Selection : PEDS·William W JaRichard W Roberts
Sep 28, 2005·Protein Engineering, Design & Selection : PEDS·Jane M Weaver-FeldhausRobert W Siegel
Sep 27, 2007·ACS Chemical Biology·Steven W MillwardRichard W Roberts
Nov 6, 2007·Frontiers in Bioscience : a Journal and Virtual Library·Philippe MondonHakim Kharrat
Dec 1, 2007·Genome Biology·Darren J SchofieldJohn McCafferty
Jan 31, 2008·Blood·Christian MenzelStefan Dübel
Apr 4, 2008·Journal of Molecular Biology·Christian W CobaughGeorge Georgiou
Oct 31, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jacob GlanvilleJaume Pons
Mar 11, 2011·Nature Biotechnology·Andrew R M BradburyJohn McCafferty
May 5, 2011·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dirk PonselKathrin Tissot
Jul 14, 2011·Protein Engineering, Design & Selection : PEDS·Chirag A PatelKevin C Wang
Dec 14, 2011·Proceedings of the National Academy of Sciences of the United States of America·Peter M BowersDavid J King
Jul 18, 2012·Protein Engineering, Design & Selection : PEDS·Narayan JayaramAndrew C R Martin
Oct 11, 2012·Journal of Nucleic Acids·Takeshi SumidaNobuhide Doi
Dec 4, 2012·Biopolymers·Matthew T WeinstockMichael S Kay
Oct 26, 2013·Drug Discovery Today·Kristopher JosephsonJack W Szostak

❮ Previous
Next ❯

Citations

Jul 31, 2016·Biochemical and Biophysical Research Communications·Masanao NakayamaNobuhide Doi
Jul 28, 2019·Applied Microbiology and Biotechnology·Linda SchwaigerlehnerRenate Kunert
Jun 25, 2021·Chemical Society Reviews·Golnaz KamaliniaRichard W Roberts

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bacteriophage: Phage Therapy

Phage therapy uses bacterial viruses (bacteriophages) to treat bacterial infections and is widely being recognized as an alternative to antibiotics. Here is the latest research.

© 2021 Meta ULC. All rights reserved