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Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
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Published on: August 9, 2019

Adnectins: engineered target-binding protein therapeutics.

D Lipovsek1

  • 1Department of Protein Design, Adnexus, Bristol-Myers Squibb R&D Company, Waltham, MA 02453, USA. dlipovsek@adnexustx.com

Protein Engineering, Design & Selection : PEDS
|November 12, 2010
PubMed
Summary
This summary is machine-generated.

Adnectins are novel therapeutic proteins derived from fibronectin. They offer antibody-like binding but are simpler to produce, with one candidate in clinical trials for cancer.

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Area of Science:

  • Protein engineering
  • Biotechnology
  • Therapeutic protein development

Background:

  • Adnectins are a new class of therapeutic proteins engineered from the tenth fibronectin type III domain.
  • They possess a unique single-domain structure, differing from antibodies but enabling high-affinity and specific target binding.
  • Adnectins offer advantages in genetic manipulation and compatibility with bacterial expression systems.

Purpose of the Study:

  • To introduce Adnectins as a novel protein scaffold for therapeutic development.
  • To highlight the design principles and advantages of Adnectins over traditional antibody-based therapeutics.
  • To present CT-322, an Adnectin targeting VEGF receptors, as a potential anti-angiogenic cancer therapy.

Main Methods:

  • Adnectins are designed based on the fibronectin type III domain structure.
  • In vitro evolution techniques such as mRNA display, phage display, and yeast display are employed for selection.
  • CT-322, a specific Adnectin, was engineered to target vascular endothelial growth factor (VEGF) receptor 2.

Main Results:

  • Adnectins demonstrate high affinity and specificity for therapeutic targets, comparable to antibodies.
  • Selected Adnectins exhibit nanomolar and picomolar binding affinities.
  • CT-322 effectively binds VEGF receptor 2 and inhibits interactions with VEGF A, C, and D.

Conclusions:

  • Adnectins represent a versatile and advantageous protein scaffold for therapeutic applications.
  • Their simplified structure and production compatibility facilitate development.
  • CT-322 shows promise as an anti-angiogenic agent, currently undergoing Phase II clinical evaluation for oncology indications.