Abstract
The increasing knowledge on the genetic basis of disease has allowed the development of promising gene-targeted therapies that can be applied to numerous diseases. Such genetic-based approaches involve the use of nucleic acids as therapeutic agents, either for the insertion or repair and regulation of specific genes. However, the clinical application of these large and charged molecules remains highly dependent on the development of delivery systems capable of mediating efficient cellular uptake. Since the first observations, two decades ago, that some protein-derived domains can translocate across biological membranes, a wide group of peptides called cellpenetrating peptides (CPPs) have been considered one of the most promising tools to improve non-invasive cellular delivery of therapeutic molecules. The mechanistic basis of CPP and CPP conjugate cellular uptake remains controversial. However, biophysical studies on the interactions of CPPs with membrane models have contributed to unravel the mechanisms underlying CPP membrane translocation as well as to propose relationships between those mechanisms and CPP efficiency in mediating cargo delivery. In this review, representative examples of CPPs were gathered from the most recent literature in order to emphasize the contributions of chemists, biophysicists and cell biologists towards the rational design of increasingly more efficient delivery systems. In this context, the present review aims at giving an overview of some of the most significant CPP families and their biological applications as nucleic acid delivery systems.
Keywords: Cell-penetrating peptides, nucleic acid delivery, CPP chemical modifications, CPP-membrane lipid interactions, cell internalization mechanisms, endosomal escape
Current Pharmaceutical Design
Title:Cell-penetrating Peptides as Nucleic Acid Delivery Systems: From Biophysics to Biological Applications
Volume: 19 Issue: 16
Author(s): Sara Trabulo, Ana L. Cardoso, Ana M. S. Cardoso, Catarina M. Morais, Amalia S. Jurado and Maria C. Pedroso de Lima
Affiliation:
Keywords: Cell-penetrating peptides, nucleic acid delivery, CPP chemical modifications, CPP-membrane lipid interactions, cell internalization mechanisms, endosomal escape
Abstract: The increasing knowledge on the genetic basis of disease has allowed the development of promising gene-targeted therapies that can be applied to numerous diseases. Such genetic-based approaches involve the use of nucleic acids as therapeutic agents, either for the insertion or repair and regulation of specific genes. However, the clinical application of these large and charged molecules remains highly dependent on the development of delivery systems capable of mediating efficient cellular uptake. Since the first observations, two decades ago, that some protein-derived domains can translocate across biological membranes, a wide group of peptides called cellpenetrating peptides (CPPs) have been considered one of the most promising tools to improve non-invasive cellular delivery of therapeutic molecules. The mechanistic basis of CPP and CPP conjugate cellular uptake remains controversial. However, biophysical studies on the interactions of CPPs with membrane models have contributed to unravel the mechanisms underlying CPP membrane translocation as well as to propose relationships between those mechanisms and CPP efficiency in mediating cargo delivery. In this review, representative examples of CPPs were gathered from the most recent literature in order to emphasize the contributions of chemists, biophysicists and cell biologists towards the rational design of increasingly more efficient delivery systems. In this context, the present review aims at giving an overview of some of the most significant CPP families and their biological applications as nucleic acid delivery systems.
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Cite this article as:
Trabulo Sara, L. Cardoso Ana, M. S. Cardoso Ana, M. Morais Catarina, S. Jurado Amalia and C. Pedroso de Lima Maria, Cell-penetrating Peptides as Nucleic Acid Delivery Systems: From Biophysics to Biological Applications, Current Pharmaceutical Design 2013; 19 (16) . https://dx.doi.org/10.2174/1381612811319160006
DOI https://dx.doi.org/10.2174/1381612811319160006 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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