Abstract
Although siRNA consist in very promising therapeutics, their clinical development is limited by several biological barriers including low cellular permeability, poor stability and lack of tissue specificity. Therefore the Achilles' heel for siRNA-based therapy is directly related to the lack of efficient system to promote their delivery. During the last two decades, cell-penetrating peptides (CPPs) have been widely developed to enhance the cellular delivery of therapeutics. In this context we have elaborated a new strategy based on selfassembling peptide-based nanoparticles. The CADY peptide is a 20-residue secondary amphipathic peptide which is able to spontaneously self associate with siRNA with a strong affinity, by combining both electrostatic and hydrophobic interactions, to form stable nanoparticles. Investigations of both physico-chemical properties and cellular siRNA delivery revealed that the CADY/siRNA complexes were able to enter a wide variety of cell lines by a mechanism independent of any endocytotic pathway. In addition a deeper understanding of the self assembly of CADY molecules around siRNA leads to a "raspberry"-like nanoparticle architecture which provides new perspectives for the CADY/siRNA formulations. Finally the robustness of the biological response infers that peptide-based nanoparticle technology holds a strong promise for therapeutic applications. The present review deals with most of the biophysical characteristics as well as the cellular mechanism and cellular applications of CADY/siRNA nanoparticles.
Keywords: Cell-penetrating peptide, CADY, siRNA, non-covalent delivery, direct translocation
Current Pharmaceutical Design
Title:Everything You Always Wanted to Know About CADY-Mediated siRNA Delivery* (* But Afraid to Ask)
Volume: 19 Issue: 16
Author(s): Karidia Konate, Anna Rydstrom, Gilles Divita and Sebastien Deshayes
Affiliation:
Keywords: Cell-penetrating peptide, CADY, siRNA, non-covalent delivery, direct translocation
Abstract: Although siRNA consist in very promising therapeutics, their clinical development is limited by several biological barriers including low cellular permeability, poor stability and lack of tissue specificity. Therefore the Achilles' heel for siRNA-based therapy is directly related to the lack of efficient system to promote their delivery. During the last two decades, cell-penetrating peptides (CPPs) have been widely developed to enhance the cellular delivery of therapeutics. In this context we have elaborated a new strategy based on selfassembling peptide-based nanoparticles. The CADY peptide is a 20-residue secondary amphipathic peptide which is able to spontaneously self associate with siRNA with a strong affinity, by combining both electrostatic and hydrophobic interactions, to form stable nanoparticles. Investigations of both physico-chemical properties and cellular siRNA delivery revealed that the CADY/siRNA complexes were able to enter a wide variety of cell lines by a mechanism independent of any endocytotic pathway. In addition a deeper understanding of the self assembly of CADY molecules around siRNA leads to a "raspberry"-like nanoparticle architecture which provides new perspectives for the CADY/siRNA formulations. Finally the robustness of the biological response infers that peptide-based nanoparticle technology holds a strong promise for therapeutic applications. The present review deals with most of the biophysical characteristics as well as the cellular mechanism and cellular applications of CADY/siRNA nanoparticles.
Export Options
About this article
Cite this article as:
Konate Karidia, Rydstrom Anna, Divita Gilles and Deshayes Sebastien, Everything You Always Wanted to Know About CADY-Mediated siRNA Delivery* (* But Afraid to Ask), Current Pharmaceutical Design 2013; 19 (16) . https://dx.doi.org/10.2174/1381612811319160004
DOI https://dx.doi.org/10.2174/1381612811319160004 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Global Expression Studies of Schizophrenic Brain: A Meta-Analysis Study Linking Neurological Immune System with Psychological Disorders
CNS & Neurological Disorders - Drug Targets Anticonvulsant Effect of the Essential Oil and Methanolic Extracts of <i>Zataria multiflora</i> Boiss
Central Nervous System Agents in Medicinal Chemistry Inhibition of G Protein-Activated Inwardly Rectifying K+ Channels by Phencyclidine
Current Neuropharmacology Post-stroke Movement Disorders: Clinical Manifestations and Pharmacological Management
Current Neuropharmacology Cognitive Identity in Schizophrenia: Vision, Space, and Body Perception from Prodrome to Syndrome
Current Psychiatry Reviews Solution NMR Study of the Transmembrane Domain of Single-Span Membrane Proteins: Opportunities and Strategies
Current Protein & Peptide Science Weight Loss in Older Persons: New Therapeutic Approaches
Current Pharmaceutical Design Impact of HLA Haplotype on the Response to Antipsychotic Treatment of Schizophrenia
Current Pharmacogenomics Clinical Trials for Neuroprotection in ALS
CNS & Neurological Disorders - Drug Targets Enhanced Action Potential Passage Through the Node of Ranvier of Myelinated Axons via Proton Hopping
Current Computer-Aided Drug Design Intracellular Bioinorganic Chemistry and Cross Talk Among Different -Omics
Current Topics in Medicinal Chemistry New Pharmacological Perspectives and Therapeutic Potential of PPAR-γ Agonists
Current Pharmaceutical Design CD164 as a Basophil Activation Marker
Current Pharmaceutical Design Gene Therapy for Parkinsons and Alzheimers Diseases: from the Bench to Clinical Trials
Current Pharmaceutical Design Editorial (Hot Topic: Neural Stem Cells and Neurodegeneration)
CNS & Neurological Disorders - Drug Targets The Novel Role for Lyn in Integrin Signaling in Human Disease
Current Signal Transduction Therapy Mitochondrial Pathology in Osteoarthritic Chondrocytes
Current Drug Targets Fighting Against Alzheimer's Disease: Synthesis of New Pyrazoline and Benzothiazole Derivatives as New Acetylcholinesterase and MAO Inhibitors
Letters in Drug Design & Discovery Models of Change in Schizophrenia: One for All, or All for Some?
Current Psychiatry Reviews Gene-Gene Interactions in a Context of Individual Variability in Antipsychotic Drug Pharmacogenomics
Current Pharmacogenomics and Personalized Medicine