Selection and Characterization of Antibodies Recognizing Unnatural Base Pairs

<b>Background</b>: Introducing unnatural base pairs into a natural, double-stranded DNA construct is a powerful tool within synthetic biology. Accordingly, the ability to detect these unnatural base pairs has many applications, including the study and detection of semisynthetic organisms...

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Main Authors: Antonietta M. Lillo, Nileena Velappan, Ruilian Wu, Madeline R. Bolding
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Biologics
Subjects:
Online Access:https://www.mdpi.com/2673-8449/4/4/26
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author Antonietta M. Lillo
Nileena Velappan
Ruilian Wu
Madeline R. Bolding
author_facet Antonietta M. Lillo
Nileena Velappan
Ruilian Wu
Madeline R. Bolding
author_sort Antonietta M. Lillo
collection DOAJ
description <b>Background</b>: Introducing unnatural base pairs into a natural, double-stranded DNA construct is a powerful tool within synthetic biology. Accordingly, the ability to detect these unnatural base pairs has many applications, including the study and detection of semisynthetic organisms. <b>Objective and Methods</b>: The work described here aimed to select human antibodies for the specific recognition of Hirao’s base pair dDs–dPn in various natural DNA contexts by using a combination of phage and yeast display technologies. <b>Results</b>: We selected a total of six antibodies in yeast-displayed scFv format, and further tested three of these antibodies in soluble form as minibodies and IgGs. We also describe an assay that can be used to detect plasmids containing dDs–dPn pair. <b>Conclusions</b>: Our antibodies did not afford the desired specificity or sensitivity for detection of a single unnatural base pair among thousands of natural. However, our data indicate not only that such detection is possible but also that these antibodies may be candidates for further affinity and specificity maturation.
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issn 2673-8449
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spelling doaj-art-576bddc2dc464de3b6d8eca7f242ea072025-08-20T02:53:27ZengMDPI AGBiologics2673-84492024-11-014442344310.3390/biologics4040026Selection and Characterization of Antibodies Recognizing Unnatural Base PairsAntonietta M. Lillo0Nileena Velappan1Ruilian Wu2Madeline R. Bolding3Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USABioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USABioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USABioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA<b>Background</b>: Introducing unnatural base pairs into a natural, double-stranded DNA construct is a powerful tool within synthetic biology. Accordingly, the ability to detect these unnatural base pairs has many applications, including the study and detection of semisynthetic organisms. <b>Objective and Methods</b>: The work described here aimed to select human antibodies for the specific recognition of Hirao’s base pair dDs–dPn in various natural DNA contexts by using a combination of phage and yeast display technologies. <b>Results</b>: We selected a total of six antibodies in yeast-displayed scFv format, and further tested three of these antibodies in soluble form as minibodies and IgGs. We also describe an assay that can be used to detect plasmids containing dDs–dPn pair. <b>Conclusions</b>: Our antibodies did not afford the desired specificity or sensitivity for detection of a single unnatural base pair among thousands of natural. However, our data indicate not only that such detection is possible but also that these antibodies may be candidates for further affinity and specificity maturation.https://www.mdpi.com/2673-8449/4/4/26unnatural base pairsHirao’s base pairrecognition of unnatural base pairsphage displayyeast displayantibody selection
spellingShingle Antonietta M. Lillo
Nileena Velappan
Ruilian Wu
Madeline R. Bolding
Selection and Characterization of Antibodies Recognizing Unnatural Base Pairs
Biologics
unnatural base pairs
Hirao’s base pair
recognition of unnatural base pairs
phage display
yeast display
antibody selection
title Selection and Characterization of Antibodies Recognizing Unnatural Base Pairs
title_full Selection and Characterization of Antibodies Recognizing Unnatural Base Pairs
title_fullStr Selection and Characterization of Antibodies Recognizing Unnatural Base Pairs
title_full_unstemmed Selection and Characterization of Antibodies Recognizing Unnatural Base Pairs
title_short Selection and Characterization of Antibodies Recognizing Unnatural Base Pairs
title_sort selection and characterization of antibodies recognizing unnatural base pairs
topic unnatural base pairs
Hirao’s base pair
recognition of unnatural base pairs
phage display
yeast display
antibody selection
url https://www.mdpi.com/2673-8449/4/4/26
work_keys_str_mv AT antoniettamlillo selectionandcharacterizationofantibodiesrecognizingunnaturalbasepairs
AT nileenavelappan selectionandcharacterizationofantibodiesrecognizingunnaturalbasepairs
AT ruilianwu selectionandcharacterizationofantibodiesrecognizingunnaturalbasepairs
AT madelinerbolding selectionandcharacterizationofantibodiesrecognizingunnaturalbasepairs