PepFect15, a novel endosomolytic cell-penetrating peptide for oligonucleotide delivery via scavenger receptors

Lindberg, Staffan; Muñoz-Alarcón, Andrés; Helmfors, Henrik; Mosqueira, Diogo; Gyllborg, Daniel; Tudoran, Oana; Langel, Ülo

doi:10.1016/j.ijpharm.2012.11.037

Cited by 46 publications

(30 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In analogous work, PepFect14 and PepFect 15 were developed for the transfection of splice-correcting oligos (Ezzat et al 2011, Lindberg et al 2013). Starting with stearylated TP10, lysines were replaced with ornithines to improve siRNA binding and also provide a higher transfection efficiency.…”

Section: Cationic Peptides For Sirna Transfectionmentioning

confidence: 99%

A role for peptides in overcoming endosomal entrapment in siRNA delivery — A focus on melittin

Hou

Pan

Schlesinger

et al. 2015

Biotechnology Advances

View full text Add to dashboard Cite

siRNA has the possibility to revolutionize medicine by enabling highly specific and efficient silencing of proteins involved in disease pathogenesis. Despite nearly 20 years of research dedicated to translating siRNA from a research tool into a clinically relevant therapeutic, minimal success has been had to date. Access to RNA interference machinery located in the cytoplasm is often overlooked, but must be considered when designing the next generation of siRNA delivery strategies. Peptide transduction domains (PTD) have demonstrated moderate siRNA transfection, which is primarily limited by endosomal entrapment. Strategies aimed at overcoming endosomal entrapment associated with peptide vectors are reviewed here, including osmotic methods, lipid conjugation, and fusogenic peptides. As an alternative to traditional PTD, the hemolytic peptide melittin exhibits the native capacity for endosomal disruption but causes cytotoxicity. However, appropriate packaging and protection of melittin with activation and release in the endosomal compartment has allowed melittin-based strategies to demonstrate both in vitro and in vivo safety and efficacy. These data suggest that melittin's membrane disruptive properties can enable safe and effective endosomolysis, building a case for melittin as a key component in a new generation of siRNA therapeutics.

show abstract

Section: Cationic Peptides For Sirna Transfectionmentioning

confidence: 99%

A role for peptides in overcoming endosomal entrapment in siRNA delivery — A focus on melittin

Hou

Pan

Schlesinger

et al. 2015

Biotechnology Advances

View full text Add to dashboard Cite

show abstract

“…al. showed for the first time that a cell surface receptor was responsible for the uptake of a CPP, the stearylated TP10 analog PepFect14 (PF14), in complex with splice correcting oligonucleotides (SCO) [12]. Later, structurally related peptides PepFect15 and NickFects in complex with oligonucleotides (ONs) (SCO and plasmid respectively) were also shown to be taken up by the same receptors, namely class A scavenger receptors (SCARA) [13,14]. These findings came from the observation that the ζ-potential of PF14:SCO complexes is not positive but negative in transfection-relevant media, making direct membrane interaction or engagement of negatively charged proteoglycans unlikely to be the initial contact due to charge repulsion.…”

Section: Introductionmentioning

confidence: 99%

A convergent uptake route for peptide- and polymer-based nucleotide delivery systems

Lindberg

Regberg

Eriksson

et al. 2015

Journal of Controlled Release

Self Cite

View full text Add to dashboard Cite

“…They were first discovered 20 years ago when it was observed that the trans-activating regulatory protein (Tat) of HIV and the third alpha-helix of antennapedia homeodomain protein (penetratin) were readily taken up by cells in vitro [73,74]. Since then many CPPs with capability to deliver cargoes intracellularly in the form of proteins, peptides, nucleic acids, nanoparticles and small molecular drugs have been characterized [75][76][77][78][79]. CPPs have been used as nanocarriers for various living cells, including plant cells, where they have been used for gene delivery into gametophytic cells [80].…”

Section: Cell-penetrating Peptides and Nanoparticlesmentioning

confidence: 99%

“…Although biophysical studies have indicated that both pathways may be involved in the uptake of cell-penetrating peptides, the mechanism of uptake of the peptide and peptide-conjugated cargoes needs to be elucidated to facilitate effective CPP-mediated drug delivery into cells. Nevertheless, CPPs have been used as nanocarriers themselves as well as in conjunction with various nanoparticles to achieve efficient cellular drug delivery both in vitro and in vivo [77,[82][83][84].…”

Section: Cell-penetrating Peptides and Nanoparticlesmentioning

confidence: 99%

Nanoparticle-Mediated Delivery of Therapeutic Drugs

Ponnappan

Chugh

2015

Pharm Med

View full text Add to dashboard Cite

Nanotechnology-based pharmaceutics is a fast emerging field in the diagnosis and therapy of a number of human diseases, including cancer. Nanoparticles offer a stable means to achieve targeted drug delivery to various cells and tissues. They have been investigated for drug delivery to different tumor tissues, to brain where the blood-brain barrier poses a significant problem in the delivery of effective therapeutic molecules, to ocular tissues and also for eliciting immune response via delivery of vaccines. Particularly, the small size of nanoparticles facilitates their easy access to a wide range of cells and tissues. Further, the size of nanoparticles can be controlled and their surface can be modified with desired ligands and receptors to specifically target cells of interest as well as achieve controlled drug release. Research is being carried out on numerous biological and synthetic nanoparticles. Diverse strategies are being developed to improve their stability, specificity and drug delivery efficiency. Nanoparticles have been also used in conjunction with cellpenetrating peptides for efficient drug delivery. Cellpenetrating peptides serve as efficient nanocarriers owing to their inherent ability to cross the plasma membrane barrier and deliver cargo to intracellular targets. Modification of nanoparticles with cell-penetrating peptides further increases their efficacy for increased permeation into varied cells and tissues. The current review focuses on different classes of nanoparticles and their application in the treatment of several types of diseases. Key PointsNanoparticle-based therapeutic drugs are widely used for the treatment of a number of diseases, including cancer.Ease of modulation of size and tuning of the nanoparticles with various ligands make them effective for formulation into specific drugs with increased therapeutic index and reduced toxicity.Successful pre-clinical and early phase clinical trials have promised the emergence of nanocarrier-based drugs.

show abstract

PepFect15, a novel endosomolytic cell-penetrating peptide for oligonucleotide delivery via scavenger receptors

Cited by 46 publications

References 29 publications

A role for peptides in overcoming endosomal entrapment in siRNA delivery — A focus on melittin

A role for peptides in overcoming endosomal entrapment in siRNA delivery — A focus on melittin

A convergent uptake route for peptide- and polymer-based nucleotide delivery systems

Nanoparticle-Mediated Delivery of Therapeutic Drugs

Contact Info

Product

Resources

About