Melittin analogs with high lytic activity at endosomal pH enhance transfection with purified targeted PEI polyplexes

Boeckle, Sabine; Fahrmeir, Julia; Röedl, Wolfgang; Ogris, Manfred; Wagner, Ernst

doi:10.1016/j.jconrel.2006.02.002

Cited by 127 publications

(108 citation statements)

References 18 publications

Supporting

Mentioning

108

Contrasting

Order By: Relevance

“…This can be attributed to the enhanced lytic activity at acidic pH, which triggered the destabilization of endosomal membranes. 109,110) The pH-sensitive fusogenic membrane peptide GALA (WEAALAEALAEALAEHLAEALAEALEALAA) was developed based on the endosomal escape mechanism of the influenza virus, an envelope-type RNA virus.…”

Section: Acceleration Of Endosomal Escape Via Membrane Fusionmentioning

confidence: 99%

The Polyethyleneglycol Dilemma: Advantage and Disadvantage of PEGylation of Liposomes for Systemic Genes and Nucleic Acids Delivery to Tumors

Hatakeyama

Akita

Harashima

2013

Biological & Pharmaceutical Bulletin

425

276

View full text Add to dashboard Cite

Gene and nucleic acid therapy is expected to play a major role in the next generation of agents for cancer treatment. We have recently developed a multifunctional envelope-type nano device (MEND) for use as a novel nonviral gene delivery system. The modification of polyethyleneglycol (PEG), i.e., PEGylation, is a useful method for achieving a longer circulation time for the delivery of MEND to a tumor via the enhanced permeability and retention (EPR) effect. However, PEGylation strongly inhibits cellular uptake and endosomal escape, which results in significant loss of activity of the delivery system. For successful nucleic acid delivery for cancer treatment, the crucial problem associated with the use of PEG, i.e., the "PEG dilemma" must be resolved. In this review, we describe the development and applications of MEND and discuss various strategies for overcoming the PEG dilemma based on the manipulation of both pharmacokinetics and intracellular trafficking of cellular uptake and endosomal release. To increase cellular uptake, target ligands including proteins, peptides, antibodies and aptamers that recognize molecules specifically expressed on tumors are first introduced. Second, cleavable PEG systems are described. The cleavage of PEG from carriers was achieved in response to the intracellular environment as well as the tumor microenvironment, which improvs cellular uptake and endosomal escape. Then, endosomal fusogenic peptides are discussed. Finally, pH-sensitive liposomes using pH-sensitive lipids are described.

show abstract

Section: Acceleration Of Endosomal Escape Via Membrane Fusionmentioning

confidence: 99%

The Polyethyleneglycol Dilemma: Advantage and Disadvantage of PEGylation of Liposomes for Systemic Genes and Nucleic Acids Delivery to Tumors

Hatakeyama

Akita

Harashima

2013

Biological & Pharmaceutical Bulletin

425

276

View full text Add to dashboard Cite

show abstract

“…6 Another cross-linking strategy uses the formation of disulfi de bonds between the thiol groups of 2 cysteine residues. McKenzie et al 7 , 21 modifi ed the CWK 18 peptide to contain Melittin GIGAVLKVLTTGLPALISWIKRKRQQ [29][30][31][32] Tat (48-60) GRKKRRQRRRPPQ [33][34][35][36][37][38] Penetratin RQIKIWFQNRRMKWKK 9,39,40 Transportan GWTLNSAGYLLGKINLKALAALAKKIL 41,42 GALA WEAALAEALAEALAEHLAEALAEALEALAA 21 systematically shortened the lysine sequence of the CWK n C peptide to determine the minimal amount of residues needed for DNA condensation and gene transfer effi ciency. The results indicated that 4 lysines fl anked by terminal cysteines were able to condense DNA with similar particle size and transfection effi ciency as a 17 lysine peptide.…”

Section: E20mentioning

confidence: 99%

“…30 Modifi cation of the C-terminally linked melittin peptide by replacement of the neutral glutamine residues (Gln25 and Gln26) with glutamic acids can increase the membrane lytic activity of these conjugates at endosomal pH. 31 Melittin has also been developed into a gene delivery peptide capable of condensing and crosslinking on DNA. 32 With the addition of lysine residues for added positive charge and terminal cysteine residues for polymerization, the hemolytic melittin peptide can be used to condense DNA into particles capable of transfecting various cell lines with an effi ciency equal to that of PEI.…”

Section: Fusogenic Peptidesmentioning

confidence: 99%

Peptide-guided gene delivery

Martin

Rice

2007

AAPS J

302

236

View full text Add to dashboard Cite

Although currently less effi cient than their viral counterparts, nonviral vectors are under intense investigation as a safer alternative for gene therapy. For successful delivery, the nonviral vector must be able to overcome many barriers to protect DNA and specifi cally deliver it for effi cient gene expression in target cells. The use of peptides as gene delivery vectors is advantageous over other nonviral agents in that they are able to achieve all of these goals. This review will focus on the application of peptides to mediate nonviral gene delivery. By examining the literature over the past 20 years, it becomes clear that no other class of biomolecules are simultaneously capable of DNA condensation, blocking metabolism, endosomal escape, nuclear localization, and receptor targeting. Based on virtually limitless diversity of peptide sequence and function information from nature, it is increasingly clear that peptide-guided gene delivery is still in its infancy.

show abstract

“…This can be attributed to the enhanced lytic activity at acidic pH, which triggered the destabilization of endosomal membranes. 21,22) Other polymers that are protonated in an intracellular acidic compartment have been reported. 23) A pH-sensitive fusogenic membrane peptide GALA (WEAALAEALAEALAEHLAEALAEALEALAA) was developed based on the endosomal escape mechanism of an influenza virus, an envelope-type RNA virus.…”

Section: Activation In Response To Endogenous/internal Stimulimentioning

confidence: 99%

Recent Advances in Endogenous and Exogenous Stimuli-Responsive Nanocarriers for Drug Delivery and Therapeutics

Hatakeyama

2017

Chem. Pharm. Bull.

View full text Add to dashboard Cite

Significant progress has been achieved in the development of stimuli-responsive nanocarriers for drug delivery, diagnosis, and therapy. Various types of triggers are utilized in the development of nanocarrier delivery. Endogenous factors such as changes in pH, redox, gradient, and enzyme concentration which are linked to disease progression have been utilized for controlling biodistribution and releasing drugs from nanocarriers, as well as increasing subsequent pharmacological activity at the disease site. Nanocarriers which respond to artificially-induced exogenous factors (such as temperature, light, magnetic field, and ultrasound) have also been developed. This review aims to discuss recent advances in the design of stimuliresponsive nanocarriers which appear to have a promising future in medicine.

show abstract

Melittin analogs with high lytic activity at endosomal pH enhance transfection with purified targeted PEI polyplexes

Cited by 127 publications

References 18 publications

The Polyethyleneglycol Dilemma: Advantage and Disadvantage of PEGylation of Liposomes for Systemic Genes and Nucleic Acids Delivery to Tumors

The Polyethyleneglycol Dilemma: Advantage and Disadvantage of PEGylation of Liposomes for Systemic Genes and Nucleic Acids Delivery to Tumors

Peptide-guided gene delivery

Recent Advances in Endogenous and Exogenous Stimuli-Responsive Nanocarriers for Drug Delivery and Therapeutics

Contact Info

Product

Resources

About