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Design of Functional Polymers for Intracellular Nucleic Acids Delivery

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Book cover Intracellular Delivery II

Part of the book series: Fundamental Biomedical Technologies ((FBMT,volume 7))

Abstract

For intracellular nucleic acid delivery, the fulfillment of certain requirements is crucial: protection of nucleic acids from enzymatic degradation in the cell exterior, efficient cellular internalization of nucleic acids, and control over intracellular distribution of nucleic acids. Polyion complex (PIC), composed of nucleic acids and polycations through electrostatic interaction, is one of the most developed delivery carriers to meet such requirements. This chapter describes rational strategies in the design of polymers for PIC-based nucleic acid delivery.

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Abbreviations

DET:

Diethylenetriamine

GSH:

Glutathione

pDNA:

Plasmid deoxyribonucleic acid

PEI:

Polyethyleneimine

PIC:

Polyion complex

siRNA:

Small interfering ribonucleic acid

SNA:

Small nucleic acid

References

  • Airenne KJ, Hu YC, Kost TA, Smith RH, Kotin RM, Ono C, Matsuura Y, Wang S, Yla-Herttuala S (2013) Baculovirus: an insect-derived vector for diverse gene transfer applications. Mol Ther 21:739–749

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Alam MR, Ming X, Fisher M, Lackey JG, Rajeev KG, Manoharan M, Juliano RL (2011) Multivalent cyclic RGD conjugates for targeted delivery of small interfering RNA. Bioconjug Chem 22:1673–1681

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bolcato-Bellemin AL, Bonnet ME, Creusat G, Erbacher P, Behr JP (2007) Sticky overhangs enhance siRNA-mediated gene silencing. Proc Natl Acad Sci USA 104:16050–16055

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Boussif O, Lezoualc’h F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr JP (1995) A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc Natl Acad Sci USA 92:7297–7301

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Carlisle RC, Etrych T, Briggs SS, Preece JA, Ulbrich K, Seymour LW (2004) Polymer-coated polyethylenimine/DNA complexes designed for triggered activation by intracellular reduction. J Gene Med 6:337–344

    Article  CAS  PubMed  Google Scholar 

  • Chen C, Okayama H (1987) High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol 7:2745–2752

    CAS  PubMed Central  PubMed  Google Scholar 

  • Demeneix B, Behr JP (2005) Polyethylenimine (PEI). Adv Genet 53:215–230

    Article  Google Scholar 

  • Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411:494–498

    Article  CAS  PubMed  Google Scholar 

  • Fischer D, Li Y, Ahlemeyer B, Krieglstein J, Kissel T (2003) In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis. Biomaterials 24:1121–1131

    Article  CAS  PubMed  Google Scholar 

  • Geiger T, Clarke S (1987) Deamidation, isomerization, and racemization at asparaginyl and aspartyl residues in peptides. Succinimide-linked reactions that contribute to protein degradation. J Biol Chem 262:785–794

    CAS  PubMed  Google Scholar 

  • Gosselin MA, Guo W, Lee RJ (2001) Efficient gene transfer using reversibly cross-linked low molecular weight polyethylenimine. Bioconjug Chem 12:989–994

    Article  CAS  PubMed  Google Scholar 

  • Hong S, Leroueil PR, Janus EK, Peters JL, Kober MM, Islam MT, Orr BG, Baker JR Jr, Banaszak Holl MM (2006) Interaction of polycationic polymers with supported lipid bilayers and cells: nanoscale hole formation and enhanced membrane permeability. Bioconjugate Chem 17:728–734

    Article  CAS  Google Scholar 

  • Itaka K, Ishii T, Hasegawa Y, Kataoka K (2010) Biodegradable polyamino acid-based polycations as safe and effective gene carrier minimizing cumulative toxicity. Biomaterials 31:3707–3714

    Article  CAS  PubMed  Google Scholar 

  • Jager M, Schubert S, Ochrimenko S, Fischer D, Schubert US (2012) Branched and linear poly(ethylene imine)-based conjugates: synthetic modification, characterization, and application. Chem Soc Rev 41:4755–4767

    Article  PubMed  Google Scholar 

  • Kanasty R, Dorkin JR, Vegas A, Anderson D (2013) Delivery materials for siRNA therapeutics. Nat Mater 12:967–977

    Article  CAS  PubMed  Google Scholar 

  • Kanayama N, Fukushima S, Nishiyama N, Itaka K, Jang WD, Miyata K, Yamasaki Y, Chung UI, Kataoka K (2006) A PEG-based biocompatible block catiomer with high buffering capacity for the construction of polyplex micelles showing efficient gene transfer toward primary cells. ChemMedChem 1:439–444

    Article  CAS  PubMed  Google Scholar 

  • Kang HC, Huh KM, Bae YH (2012) Polymeric nucleic acid carriers: current issues and novel design approaches. J Control Release 164:256–264

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kataoka K, Harada A, Nagasaki Y (2001) Block copolymer micelles for drug delivery: design, characterization and biological significance. Adv Drug Deliv Rev 47:113–131

    Article  CAS  PubMed  Google Scholar 

  • Kim YH, Park JH, Lee M, Kim YH, Park TG, Kim SW (2005) Polyethylenimine with acid-labile linkages as a biodegradable gene carrier. J Control Release 103:209–219

    Article  CAS  PubMed  Google Scholar 

  • Knorr V, Ogris M, Wagner E (2008) An acid sensitive ketal-based polyethylene glycol-oligoethylenimine copolymer mediates improved transfection efficiency at reduced toxicity. Pharm Res 25:2937–2945

    Article  CAS  PubMed  Google Scholar 

  • Kunath K, von Harpe A, Fischer D, Petersen H, Bickel U, Voigt K, Kissel T (2003) Low-molecular-weight polyethylenimine as a non-viral vector for DNA delivery: comparison of physicochemical properties, transfection efficiency and in vivo distribution with high-molecular-weight polyethylenimine. J Control Release 89:113–125

    Article  CAS  PubMed  Google Scholar 

  • Lee SH, Mok H, Park TG (2011) Di- and triblock siRNA-PEG copolymers: PEG density effect of polyelectrolyte complexes on cellular uptake and gene silencing efficiency. Macromol Biosci 11:410–418

    Article  CAS  PubMed  Google Scholar 

  • Meister A, Anderson ME (1983) Glutathione. Annu Rev Biochem 52:711–760

    Article  CAS  PubMed  Google Scholar 

  • Miyata K, Oba M, Nakanishi M, Fukushima S, Yamasaki Y, Koyama H, Nishiyama N, Kataoka K (2008) Polyplexes from poly(aspartamide) bearing 1,2-diaminoethane side chains induce pH-selective, endosomal membrane destabilization with amplified transfection and negligible cytotoxicity. J Am Chem Soc 130:16287–16294

    Article  CAS  PubMed  Google Scholar 

  • Miyata K, Nishiyama N, Kataoka K (2012) Rational design of smart supramolecular assemblies for gene delivery: chemical challenges in the creation of artificial viruses. Chem Soc Rev 41:2562–2574

    Article  CAS  PubMed  Google Scholar 

  • Mok H, Lee SH, Park JW, Park TG (2010) Multimeric small interfering ribonucleic acid for highly efficient sequence-specific gene silencing. Nat Mater

    Google Scholar 

  • Palte MJ, Raines RT (2012) Interaction of nucleic acids with the glycocalyx. J Am Chem Soc 134:6218–6223

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ramishetti S, Huang L (2012) Intelligent design of multifunctional lipid-coated nanoparticle platforms for cancer therapy. Ther Deliv 3:1429–1445

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Saito G, Swanson JA, Lee KD (2003) Drug delivery strategy utilizing conjugation via reversible disulfide linkages: role and site of cellular reducing activities. Adv Drug Deliv Rev 55:199–215

    Article  CAS  PubMed  Google Scholar 

  • Scholz C, Wagner E (2012) Therapeutic plasmid DNA versus siRNA delivery: common and different tasks for synthetic carriers. J Controlled Release 161:554–565

    Article  CAS  Google Scholar 

  • Sonawane ND, Szoka FC Jr, Verkman AS (2003) Chloride accumulation and swelling in endosomes enhances DNA transfer by polyamine-DNA polyplexes. J Biol Chem 278:44826–44831

    Article  CAS  PubMed  Google Scholar 

  • Suh J, Paik HJ, Hwang BK (1994) Ionization of poly(ethylenimine) and poly(allylamine) at various pH’s. Bioorg Chem 22:318–327

    Article  CAS  Google Scholar 

  • Suma T, Miyata K, Ishii T, Uchida S, Uchida H, Itaka K, Nishiyama N, Kataoka K (2012) Enhanced stability and gene silencing ability of siRNA-loaded polyion complexes formulated from polyaspartamide derivatives with a repetitive array of amino groups in the side chain. Biomaterials 33:2770–2779

    Article  CAS  PubMed  Google Scholar 

  • Takemoto H, Ishii A, Miyata K, Nakanishi M, Oba M, Ishii T, Yamasaki Y, Nishiyama N, Kataoka K (2010) Polyion complex stability and gene silencing efficiency with a siRNA-grafted polymer delivery system. Biomaterials 31:8097–8105

    Article  CAS  PubMed  Google Scholar 

  • Takemoto H, Miyata K, Hattori S, Ishii T, Suma T, Uchida S, Nishiyama N, Kataoka K (2013) Acidic pH-responsive siRNA conjugate for reversible carrier stability and accelerated endosomal escape with reduced IFNα-associated immune response. Angew Chem Int Ed 52:6218–6221

    Article  CAS  Google Scholar 

  • Thomas M, Klibanov AM (2002) Enhancing polyethylenimine’s delivery of plasmid DNA into mammalian cells. Proc Natl Acad Sci USA 99:14640–14645

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Uchida H, Miyata K, Oba M, Ishii T, Suma T, Itaka K, Nishiyama N, Kataoka K (2011) Odd-even effect of repeating aminoethylene units in the side chain of N-substituted polyaspartamides on gene transfection profiles. J Am Chem Soc 133:15524–15532

    Article  CAS  PubMed  Google Scholar 

  • Zhang M, Kataoka K (2009) Nano-structured composites based on calcium phosphate for cellular delivery of therapeutic and diagnostic agents. Nano Today 4:508–517

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, R1-11, 4259 Nagatsuta, Midori-ku, Yokohama, 226-8503, Japan

    Hiroyasu Takemoto & Nobuhiro Nishiyama

Authors
  1. Hiroyasu Takemoto
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  2. Nobuhiro Nishiyama
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Corresponding author

Correspondence to Nobuhiro Nishiyama .

Editor information

Editors and Affiliations

  1. Chemical and Biological Engineering, Vanderbilt University, Nashville, Tennessee, USA

    Aleš Prokop

  2. Chemistry and Materials Engineering, Kansai University, Osaka, Japan

    Yasuhiko Iwasaki

  3. Department of Applied Chemistry, Osaka Prefecture University, Osaka, Japan

    Atsushi Harada

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Takemoto, H., Nishiyama, N. (2014). Design of Functional Polymers for Intracellular Nucleic Acids Delivery. In: Prokop, A., Iwasaki, Y., Harada, A. (eds) Intracellular Delivery II. Fundamental Biomedical Technologies, vol 7. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8896-0_10

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