Delivery of Nucleic Acids and Gene Delivery

Akita, Hidetaka; Hatakeyama, Hiroto; Khalil, Ikramy A.; Yamada, Yuma; Harashima, Hideyoshi

doi:10.1016/b978-0-08-055294-1.00150-1

Cited by 9 publications

(10 citation statements)

References 465 publications

(331 reference statements)

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“…The polymers can be further functionalized with target‐specific sequences for cytosolic or nuclear delivery. Moreover, in contrast to viral systems, non‐viral polymers are capable of delivering different types of nucleic acids such as pDNA, siRNA, and miRNA …”

Section: Discussionmentioning

confidence: 99%

“…Moreover, in contrast to viral systems, non-viral polymers are capable of delivering different types of nucleic acids such as pDNA, siRNA, and miRNA. 28 In our design, we took advantage of the cationic nature of the lysine groups adjacent to the spider silk domain together with the hMSCs receptor-specific targeting capabilities of the HAB peptide to improve gene delivery towards hMSCs. It was recently demonstrated by Santos and coworkers that the HAB peptide can be specifically recognized by hMSCs.…”

Section: Discussionmentioning

confidence: 99%

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Multifunctional spider silk polymers for gene delivery to human mesenchymal stem cells

2014

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Non-viral gene delivery systems are important transport vehicles that can be safe and effective alternatives to currently available viral systems. A new family of multifunctional spider silk-based gene carriers was bioengineered and found capable of targeting human mesenchymal stem cells (hMSCs). These carriers successfully delivered DNA to the nucleus of these mammalian cells. The presence of specific functional sequences in the recombinant proteins, such as a nuclear localization sequence (NLS) of the large tumor (T) antigen of the Simian virus 40 (SV40), an hMSC high affinity binding peptide (HAB), and a translocation motif (TLM) of the hepatitis-B virus surface protein (PreS2), and their roles in mitigation and enhancement of gene transfection efficiency towards hMSCs were characterized. The results demonstrate that these bioengineered spider silk proteins serve as effective carriers, without the well-known complications associated with viral delivery systems.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Multifunctional spider silk polymers for gene delivery to human mesenchymal stem cells

2014

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“…Selected examples of viral and non-viral delivery systems that have been explored to deliver therapeutic miRNAs and siRNAs both in vivo and in vitro are summarized in Table 1 and Table 2, respectively. For a better understanding of the nucleic acids and gene delivery, please refer to the chapter summarized by Akita et al (2011) The first clinical trial of a miRNA therapy began in 2013, with the second one starting in early 2015. In contrast, the first clinical trial of a siRNA therapeutic was initiated in 2004 (Ozcan et al, 2015).…”

Section: Summary Of Delivery Systems and Clinical Status In Small Nonmentioning

confidence: 99%

Small non-coding RNAs-based bone regulation and targeting therapeutic strategies

Yang

Fang

2017

Molecular and Cellular Endocrinology

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Small non-coding RNAs, which are 20-25 nucleotide ribonucleic acids, have emerged as an important transformation in the biological evolution over almost three decades. microRNAs (miRNAs) and short interfering RNAs (siRNAs) are two significant categories of the small RNAs that exert important effects on bone endocrinology and skeletology. Therefore, clarifying the expression and function of these important molecules in bone endocrine physiology and pathology is of great significance for improving their potential therapeutic value for metabolism-associated bone diseases. In the present review, we highlight the recent advances made in understanding the function and molecular mechanism of these small non-coding RNAs in bone metabolism, especially their potentially therapeutic values in bone-related diseases.

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“…A highly readable accounts of the topic are available (Kaneda 2001;Lechardeur and Lukacs 2002;Wiethoff and Middaugh 2003;Read et al 2005;Oupický 2005;Kabanov 2006;Wang et al 2012;Nguyen and Szoka 2012;Kamimura et al 2012). Various biological barriers for gene carriers were reviewed also by Akita et al (2011). Excess of positive charges allows electrostatic interactions with negatively charged surfaces of the target cells.…”

Section: Introductionmentioning

confidence: 98%

“…These genosomes are formed through compaction of DNA and charge neutralization and aggregation of macromolecular complexes, leading to formation of multilamellar structures (Zuidam et al 1999;Yan et al 2012). Various types of therapeutic single stranded, double stranded and hybrid nucleic acids have been designed for therapeutic gene delivery, such as plasmid DNA, oligodeoxyribonucleotides, small interference RNA (siRNA) and micro RNA (miRNA) (Akita et al 2011). Whatever nucleic acid chain topology is used (Dhanoya et al 2011), these macromolecular therapeutic assemblies should reach either the cytosol or the nucleus of target cells before successful transgene expression.…”

Section: Introductionmentioning

confidence: 99%

Supramolecular Langmuir monolayers and multilayered vesicles of self-assembling DNA–lipid surface structures and their further implications in polyelectrolyte-based cell transfections

2015

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The basic interfacial characteristics of DNA-lipid recognitions have been studied. The complex structures of individual unbound DNA molecules and their binary and ternary complexes with zwitterionic lipids and divalent cations were followed by employing lipid monolayers at the air-liquid interfaces, as well as by performing various microscopic, spectroscopic, and thermodynamic measurements with multilayered vesicles. The pressure-area isotherms depicted that Mg 2? -ions increase the surface pressure of lipid films and thus give rise to electrostatic and hydrophobic lipid-DNA interactions in terms of DNA adsorption, adhesion, and compaction. These features were further approached by using multilamellar vesicles with a mean diameter of 850 nm, where a metal ion-directed nucleic acid compaction and condensation effects were shown. The data obtained show the effectiveness of Langmuir monolayers and lipid multilayers in studying nucleic acid-lipid recognitions. The data provide with further details and support previous reports on mainly structural features of these recognitions. Biomolecular surface recognition events were presented in direct link with spectral and thermodynamic features of lipid vesicle-polynucleotide complex formations. The results serve to build a theoretical model considering the use of neutral lipids in lipoplex designs as a polyelectrolyte alternatives to the currently employed cytotoxic cationic liposomes. The supramolecular structures formed and their possible roles in interfacial electrostatic and hydrophobic mechanisms of endosomal escape in relevant cell transfection assays are particularly emphasized.

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Delivery of Nucleic Acids and Gene Delivery

Cited by 9 publications

References 465 publications

Multifunctional spider silk polymers for gene delivery to human mesenchymal stem cells

Multifunctional spider silk polymers for gene delivery to human mesenchymal stem cells

Small non-coding RNAs-based bone regulation and targeting therapeutic strategies

Supramolecular Langmuir monolayers and multilayered vesicles of self-assembling DNA–lipid surface structures and their further implications in polyelectrolyte-based cell transfections

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