Development of Elastin-like Polypeptide for Targeted Specific Gene Delivery in Vivo

Overview

Journal J Nanobiotechnology

Publisher Biomed Central

Specialty Biotechnology

Date 2020 Jan 19

PMID 31952530

Citations 15

Authors

Aena Yi

Dahye Sim

Young-Jin Lee

Vijaya Sarangthem

Rang-Woon Park

Affiliations

Soon will be listed here.

Abstract

Background: The successful deliveries of siRNA depend on their stabilities under physiological conditions because greater in vivo stability enhances cellular uptake and enables endosomal escape. Viral-based systems appears as most efficient approaches for gene delivery but often compromised in terms of biocompatibility, patient safety and high cost scale up process. Here we describe a novel platform of gene delivery by elastin-like polypeptide (ELP) based targeting biopolymers.

Results: For better tumor targeting and membrane penetrating characteristics, we designed various chimeric ELP-based carriers containing a cell penetrating peptide (Tat), single or multiple copies of AP1 an IL-4 receptor targeting peptide along with coding sequence of ELP and referred as Tat-AE or Tat-AV. These targeted polypeptides were further analyzed for its ability to deliver siRNA (Luciferase gene) in tumor cells in comparison with non-targeted controls (Tat-E or E). The positively charged amino acids of these polypeptides enabled them to readily complex with negatively charged nucleic acids. The complexation of nucleic acid with respective polypeptides facilitated its transfection efficiency as well as stability. The targeted polypeptides (Tat-AE or Tat-AV) selectively delivered siRNA into tumor cells in a receptor-specific fashion, achieved endosomal and lysosomal escape, and released gene into cytosol. The target specific delivery of siRNA by Tat-AE or Tat-AV was further validated in murine breast carcinoma 4T1 allograft mice model.

Conclusion: The designed delivery systems efficiently delivered siRNA to the target site of action thereby inducing significant gene silencing activity. The study shows Tat and AP1 functionalized ELPs constitute a novel gene delivery system with potential therapeutic applications.

Citing Articles

Development of an Elastin-like Polypeptide-Based Nucleic Acid Delivery System Targeted to EGFR+ Bladder Cancer Cells Using a Layer-by-Layer Approach.

Aayush A, Darji S, Estes K, Yeh E, Thompson D Biomacromolecules. 2024; 25(9):5729-5744.

PMID: 39185801 PMC: 11388462. DOI: 10.1021/acs.biomac.4c00165.

Protein-based nanoparticles for therapeutic nucleic acid delivery.

Eweje F, Walsh M, Ahmad K, Ibrahim V, Alrefai A, Chen J Biomaterials. 2024; 305:122464.

PMID: 38181574 PMC: 10872380. DOI: 10.1016/j.biomaterials.2023.122464.

Application of bioengineered elastin-like polypeptide-based system for targeted gene delivery in tumor cells.

Yi A, Sim D, Lee S, Sarangthem V, Park R Biomater Biosyst. 2023; 6:100050.

PMID: 36824163 PMC: 9934475. DOI: 10.1016/j.bbiosy.2022.100050.

Engineered elastin-like polypeptides: An efficient platform for enhanced cancer treatment.

Jiang A, Guan X, He L, Guan X Front Pharmacol. 2023; 13:1113079.

PMID: 36699056 PMC: 9868590. DOI: 10.3389/fphar.2022.1113079.

Impact of aromatic residues on the intrinsic disorder and transitional behaviour of model IDPs.

Garcia-Arevalo C, Quintanilla-Sierra L, Santos M, Ferrero S, Acosta S, Rodriguez-Cabello J Mater Today Bio. 2022; 16:100400.

PMID: 36060106 PMC: 9434135. DOI: 10.1016/j.mtbio.2022.100400.

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