Polyamidoamine Dendrimer Conjugates with Cyclodextrins as Novel Carriers for DNA, shRNA and siRNA

Hidetoshi Arima,Taishi Higashi,Keiichi Motoyama

doi:10.3390/pharmaceutics4010130

Hidetoshi Arima, Taishi Higashi + Show 1 more

Open Access

https://doi.org/10.3390/pharmaceutics4010130

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Journal: Pharmaceutics	Publication Date: Feb 1, 2012
Citations: 91	License type: CC BY 4.0

Affiliation: Kumamoto University

Abstract

Gene, short hairpin RNA (shRNA) and small interfering RNA (siRNA) delivery can be particularly used for the treatment of diseases by the entry of genetic materials mammalian cells either to express new proteins or to suppress the expression of proteins, respectively. Polyamidoamine (PAMAM) StarburstTM dendrimers are used as non-viral vectors (carriers) for gene, shRNA and siRNA delivery. Recently, multifunctional PAMAM dendrimers can be used for the wide range of biomedical applications including intracellular delivery of genes and nucleic acid drugs. In this context, this review paper provides the recent findings on PAMAM dendrimer conjugates with cyclodextrins (CyDs) for gene, shRNA and siRNA delivery.

Highlights

Gene therapy has been utilized for vaccination and for the treatment of several diseases, such as genetic diseases, cancers, cardiovascular diseases, infectious diseases and dermatological diseases [1,2].Approximately 500 clinical trials of gene therapy have been performed in the world from 2006 to 2010[3]
These results suggest the potential use of α-CyD Conjugates with Dendrimer (α-CDE) (G3, degree of substitution (DS) 2) as a promising non-viral vector in vitro and in vivo, and these data may be useful for design of α-CyD conjugates with other non-viral vectors, the further modification of the chemical structure of α-CDE (G3, DS 2) is required to improve the carrier’s ability
Β-CDE (G2, DS 1.3), 1.3) systems to A549 and RAW264.7 cells. These results suggest that some factors except for the physicochemical properties, enzymatic stability and cellular uptake of the plasmid DNA (pDNA) complex with GUG-β-CDE (G2, DS 1.8) may be strongly involved in high gene transfer activity of GUG-β-CDE (G2, DS 1.8), compared to α-CDE (G2, DS 1.2) and β-CDE (G2, DS 1.3)

Summary

Introduction

Gene therapy has been utilized for vaccination and for the treatment of several diseases, such as genetic diseases, cancers, cardiovascular diseases, infectious diseases and dermatological diseases [1,2].Approximately 500 clinical trials of gene therapy have been performed in the world from 2006 to 2010[3]. These results suggest that some factors other than physicochemical properties or cellular uptake of pDNA complexes with α-CDE (G3, DS 2) may be potently associated with improving gene transfer activity. These results suggest that some factors except for the physicochemical properties, enzymatic stability and cellular uptake of the pDNA complex with GUG-β-CDE (G2, DS 1.8) may be strongly involved in high gene transfer activity of GUG-β-CDE (G2, DS 1.8), compared to α-CDE (G2, DS 1.2) and β-CDE (G2, DS 1.3).

Results

Conclusion