A small, synthetic peptide for gene delivery via the serpin-enzyme complex receptor

Abstract

A small (33 amino acid), bifunctional, synthetic peptide represents a highly efficient and readily standardised DNA vector for the SECR. The effectiveness of this peptide depends on the distance of the K16 moiety from the targeting ligand. High salt concentrations are not required to form effective vector/DNA complexes.

The in vivo use of chloroquine to promote non‐viral gene delivery to the liver via the portal vein and bile duct

“…In non-ionic isotonic solutions such as 5% dextrose, vector/DNA complexes form smaller particles and are more stable than in physiological salt solutions, to DNA concentrations of 50 µg/ml [27]. Figure 6a shows that vector/DNA complexes at 10 µg/ml of DNA were much less effective than at 50 µg/ml of DNA, clearly demonstrating the importance of DNA dose.…”

“…Moreover, the problem of aggregation of vector/DNA complexes in physiological salt solutions at high (100 µg/ml) concentrations of DNA has been previously noted [27]. In non-ionic isotonic solutions such as 5% dextrose, vector/DNA complexes form smaller particles and are more stable than in physiological salt solutions, to DNA concentrations of 50 µg/ml [27].…”

“…The systemic intravenous or portal vein administration of naked DNA, in association with various osmotic and pressure shocks, has been shown to deliver genes to hepatocytes [27,28]. Our protocol for administration of 50 µg/ml of naked DNA through a branch of the portal vein would give optimal exposure of the liver lobule to the DNA, but without osmotic or pressure shocks.…”

Use of Synthetic Peptides for Non-viral Gene Delivery

“…The serpin-enzyme complex receptor (SECR) was successfully targeted for gene delivery using peptide ligands covalently linked with oligolysine (Patel et al 2001). The authors found that the peptide [K] 16 CSIPPEVKFNKPFVFLI forms small complexes with DNA and showed high transfection efficiency in an Huh-7 human hepatocyte cell line expressing the receptor.…”

Peptide delivery systems

“…Some of the reasons for using peptides for gene delivery include: versatile synthetic technique, accurate determination of the molecular structure, purity of the reagent and flexibility [26]. In a recent study by Patel et al [27] a small bifunctional peptide (K16CSIPPEVKFNKPFVFLI) was used for gene delivery to the HUH7 human hepatocyte cell line. It was shown by laser scattering techniques that this peptide binds to and condenses DNA into small particles.…”