Twist Bioscience Publishes Data on VHH Single Domain Antibody Discovery Using New Methodology on Optofluidic Platform
15 February 2023 - 12:00AM
Business Wire
Demonstrates Ability to Generate Humanized
PSMA-Specific VHH Single Domain Antibodies via Single B Cell
Screening on the Beacon Platform
Twist Bioscience Corporation (NASDAQ: TWST), a company enabling
customers to succeed through its offering of high-quality synthetic
DNA using its silicon platform, today published on the successful
discovery of alpaca-derived VHH antibodies using a disruptive,
function-forward in vivo discovery workflow developed by Abveris,
also known as Twist Boston, on the Beacon optofluidic platform. The
paper, titled “Alpaca Single B Cell Interrogation and
Heavy-Chain-Only Antibody Discovery on an Optofluidic Platform,”
was published in BioRxiv.
“In vivo discovery approaches for VHH antibodies have been
limited by the lack of methodologies available for camelid B cell
interrogation to discover heavy-chain-only antibodies. Twist Boston
developed highly sophisticated assay formats for use on the Beacon
optofluidic platform, which can enable the enrichment and screening
of alpaca B cells in a way that provides in-depth functional data
from each cell,” said Emily M. Leproust, Ph.D., CEO and co-founder
of Twist Bioscience. “We are able to offer customers in vivo and
library based VHH antibody discovery and optimization approaches,
providing them with integrated solutions to identify VHH and other
antibodies with improved characteristics, such as higher binding
affinity and functional activity for difficult targets.”
A VHH single domain antibody is the antigen binding domain from
unique heavy-chain-only antibodies generated in camelids such as
llamas and alpacas. Most antibodies contain two variable domains,
the heavy and the light chains; however, camelids make antibodies
containing just a heavy chain, from which the VHH single domain is
derived. The small size of the VHH single domain antibodies allow
them to access targets that traditional antibodies cannot, with
tight binding affinities and high specificity. In addition, the
lack of a paired light chain in VHH single domain antibodies
simplifies downstream engineering, accelerating development
timelines.
In this proof-of-concept study, custom enrichment, culture,
detection, and sequencing methods were used to screen single B
cells directly from immunized alpacas for target specificity and
heavy-chain-only antibody secretion from alpacas immunized with two
different targets, either human prostate specific membrane antigen
(PSMA) or a second blinded target. B cells secreting
target-specific heavy-chain-only antibodies were identified,
exported, and sequenced.
PSMA-specific VHH hits were recombinantly expressed as VHH-Fc,
purified, and characterized using label-free techniques. All but
one VHH-Fc bound PSMA with a single-digit nanomolar affinity. Four
VHH candidates were successfully humanized in silico using a rapid
bulk humanization approach powered by machine learning.
Next-generation repertoire sequencing of PBMCs harvested at
longitudinal timepoints throughout immunization was also performed.
This uncovered additional variants within the clonal lineages of
the validated hits, some of which could potentially exhibit
superior pharmacological properties.
This unique combination of repertoire sequencing and
function-forward single B cell screening could be used for antibody
optimization by leveraging Twist’s library design platform to
generate antigen-biased VHH single domain libraries to discover
superior variants. In addition, functional validation of these
optimized lead candidates could enable downstream development of
high quality PSMA-specific VHH single domain antibodies for
therapeutic or diagnostic purposes.
About Twist Bioscience Corporation
Twist Bioscience is a leading and rapidly growing synthetic
biology and genomics company that has developed a disruptive DNA
synthesis platform to industrialize the engineering of biology. The
core of the platform is a proprietary technology that pioneers a
new method of manufacturing synthetic DNA by “writing” DNA on a
silicon chip. Twist is leveraging its unique technology to
manufacture a broad range of synthetic DNA-based products,
including synthetic genes, tools for next-generation sequencing
(NGS) preparation, and antibody libraries for drug discovery and
development. Twist is also pursuing longer-term opportunities in
digital data storage in DNA and biologics drug discovery. Twist
makes products for use across many industries including healthcare,
industrial chemicals, agriculture and academic research.
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Twist Bioscience Legal Notice Regarding Forward-Looking
Statements
This press release contains forward-looking statements. All
statements other than statements of historical facts contained
herein are forward-looking statements reflecting the current
beliefs and expectations of management made pursuant to the safe
harbor provisions of the Private Securities Litigation Reform Act
of 1995, including, but not limited to, statements regarding the
ability of the new methodology to be used for VHH single domain
antibody optimization. Forward-looking statements involve known and
unknown risks, uncertainties, and other important factors that may
cause Twist Bioscience’s actual results, performance, or
achievements to be materially different from any future results,
performance, or achievements expressed or implied by the
forward-looking statements. Such risks and uncertainties include,
among others, the risks and uncertainties relating to COVID-19; the
ability to attract new customers and retain and grow sales from
existing customers; risks and uncertainties of rapidly changing
technologies and extensive competition in synthetic biology that
could make the products Twist Bioscience is developing obsolete or
non-competitive; uncertainties of the retention of significant
customers; the ability of Twist Bioscience to successfully
integrate acquired companies, including Abveris, and to achieve
expected benefits from acquisitions; supply chain and other
disruptions caused by the COVID-19 pandemic or otherwise; risks of
third party claims alleging infringement of patents and proprietary
rights or seeking to invalidate Twist Bioscience’s patents or
proprietary rights; and the risk that Twist Bioscience’s
proprietary rights may be insufficient to protect its technologies.
For a description of the risks and uncertainties that could cause
actual results to differ from those expressed in these
forward-looking statements, as well as risks relating to Twist
Bioscience’s business in general, see Twist Bioscience’s risk
factors set forth in Twist Bioscience’s Quarterly Report on Form
10-Q filed with the Securities and Exchange Commission on February
7, 2023 and subsequent filings with the SEC. Any forward-looking
statements contained in this press release speak only as of the
date hereof, and Twist Bioscience specifically disclaims any
obligation to update any forward-looking statement, whether as a
result of new information, future events or otherwise.
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For Twist Bioscience: Angela Bitting SVP, Corporate
Affairs 925- 202-6211 abitting@twistbioscience.com
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