Development of a Nature-Inspired Vector for Targeted Systemic Breast Cancer Gene Therapy

Abstract

The purpose of this research was to develop a gene delivery system that can target breast cancer cells specifically and transfect them efficiently. Using component integration approach, several subsystems of diverse biological origin were integrated onto a modular platform in order to carry diverse functions of an efficient gene delivery vehicle. A biomimetic vector was genetically engineered to contain at precise locations: a) an adenovirus peptide to condense pDNA into nanosize particles, b) a combinatorially-screened synthetic peptide to target breast cancer cells and enhance internalization of nanoparticles, c) a pH-responsive synthetic fusogenic peptide to disrupt endosome membranes and facilitate escape of the nanoparticles into the cytosol, and d) a nuclear localization signal from human immuno-deficiency virus for microtubule mediated transfer of genetic material to the nucleus. The vector was characterized physicochemically and biologically and the results demonstrated that a fully functional vector can be engineered to target specificity, mimic virus characteristics and overcome the targeted gene transfer.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2008
Accession Number
ADA493871

Entities

People

  • Arash Hatefi

Organizations

  • Washington State University

Tags

DTIC Thesaurus Topics

  • Blood
  • Breast Cancer
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Cytoplasm
  • Cytoskeleton
  • Department Of Defense
  • Gene Delivery
  • Gene Therapy
  • Materials
  • Neoplasms
  • Particles
  • Proteins
  • Therapy
  • Virotherapy
  • Viruses

Fields of Study

  • Biology

Readers

  • Molecular Genetics
  • Nanocomposite Materials Science

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech