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Engineered protein inhibitors for precise targeting of matrix metalloproteinases

  • Naama Rotenberg
  • , Noam Y. Bentolila
  • , Julia M. Shifman*
  • *Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

Matrix metalloproteinases (MMPs) are a family of 23 zinc-dependent proteases involved in extracellular matrix (ECM) remodeling and are implicated in diseases such as cancer, arthritis, and cardiovascular disorders. Broad-spectrum MMP inhibitors (MMPIs) have proven counterproductive due to the protective roles of certain MMPs and their expression in healthy tissues. Recent advances in protein engineering have enabled the development of highly specific protein-based MMPIs that precisely target individual MMPs. These engineered proteins, often derived from antibody fragments or endogenous MMPIs, offer enhanced selectivity, reduced off-target effects, and improved therapeutic efficacy. This review highlights novel strategies for the precise targeting of MMPs using engineered proteins and discusses their potential to transform diagnostics and treatment of MMP-driven diseases.

Original languageEnglish
Pages (from-to)919-930
Number of pages12
JournalTrends in Biochemical Sciences
Volume50
Issue number10
DOIs
StatePublished - Oct 2025

Bibliographical note

Publisher Copyright:
© 2025 Elsevier Ltd

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Keywords

  • antibodies
  • matrix metalloproteinase inhibitors (MMPIs)
  • matrix metalloproteinases (MMP)
  • protein engineering
  • protein-based therapeutics
  • tissue inhibitors of matrix metalloproteinases (TIMPs)

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