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Carbohydrate Polymers for Nonviral Nucleic Acid Delivery

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Book cover Nucleic Acid Transfection

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 296))

Abstract

Carbohydrates have been investigated and developed as delivery vehicles for shuttling nucleic acids into cells. In this review, we present the state of the art in carbohydrate-based polymeric vehicles for nucleic acid delivery, with the focus on the recent successes in preclinical models, both in vitro and in vivo. Polymeric scaffolds based on the natural polysaccharides chitosan, hyaluronan, pullulan, dextran, and schizophyllan each have unique properties and potential for modification, and these results are discussed with the focus on facile synthetic routes and favorable performance in biological systems. Many of these carbohydrates have been used to develop alternative types of biomaterials for nucleic acid delivery to typical polyplexes, and these novel materials are discussed. Also presented are polymeric vehicles that incorporate copolymerized carbohydrates into polymer backbones based on polyethylenimine and polylysine and their effect on transfection and biocompatibility. Unique scaffolds, such as clusters and polymers based on cyclodextrin (CD), are also discussed, with the focus on recent successes in vivo and in the clinic. These results are presented with the emphasis on the role of carbohydrate and charge on transfection. Use of carbohydrates as molecular recognition ligands for cell-type specific delivery is also briefly reviewed. We contend that carbohydrates have contributed significantly to progress in the field of non-viral DNA delivery, and these new discoveries are impactful for developing new vehicles and materials for treatment of human disease.

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Abbreviations

APC:

Antigen-presenting cell

apoB:

Apolipoprotein B

ASF:

Asialofetuin

ASGP:

Asialoglycoprotein receptor

AS-ODN:

Antisense oligodeoxynucleotide

CD:

Cyclodextrin

CDI:

1,1'-Carbonyldiimidazole

CDP:

Cyclodextrin-containing polycations

CPP:

Cell penetrating peptide

DCC:

N,N'-Dicyclohexylcarbodiimide

DDMC:

2-Diethyl-aminoethyl–dextran–methyl methacrylate graft copolymer

DEAE:

2-Diethyl-aminoethyl

DMEM:

Dulbecco’s Modified Eagle Medium

EDC:

1-Ethyl-3-(3-dimethyl amino)propyl carbodiimide

EtiBr:

Ethidium bromide

HA:

Hyaluronic acid

IL:

Interleukin

N4C3:

Tripropylenetetramine

NHS:

N-Hydroxysuccinimide

NPC:

Non-parenchymal

PAMAM:

Polyamidoamine

PBS:

Phosphate buffered saline

PC:

Parenchymal

PDGF:

Platelet-derived growth factor

PEG:

Poly(ethylene glycol)

PEI:

Polyethylenimine

PGP:

PEGylated glycopeptide

PLGA:

Poly(lactide-co-glycolide)

PLL:

Poly-l-lysine

PO-DNA:

Phosphodiester-DNA

poly(A):

Polyadenine

poly(C):

Polycytosine

poly(dA):

Polydeoxyadenine

poly(dT):

Polydeoxythymine

PS-DNA:

Phosphorothioate-DNA

PVP:

Poly(vinylpyrrolidone)

R8:

Octaarginine

RGD:

Arginine-glycine-aspartic acid

SMC:

Smooth muscle cell

SPG:

Schizophyllan

TNF:

Tumor necrosis factor

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Acknowledgments

We apologize to our many colleagues whose elegant work we were unable to discuss directly in this review. The authors acknowledge NIH New Innovator Award. T.M.R. is a fellow of the Alfred P. Sloan Research Foundation and a recipient of the Camille Dreyfus Teacher-Scholar Award.

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Authors and Affiliations

  1. Department of Chemistry, Macromolecules and Interfaces Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA, 24060, USA

    Antons Sizovs, Patrick M. McLendon & Theresa M. Reineke

  2. Department of Chemistry, University of Cincinnati, Cincinnati, OH, 45229, USA

    Sathya Srinivasachari

  3. Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, India

    Sathya Srinivasachari

  4. Department of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 45228, USA

    Patrick M. McLendon

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  1. Antons Sizovs
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  2. Patrick M. McLendon
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  4. Theresa M. Reineke
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Correspondence to Theresa M. Reineke .

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  1. Cell Biology/RNAi, QIAGEN GmbH, Qiagen Str. 1, Hilden, 40724, Germany

    Wolfgang Bielke

  2. Cell Biology/RNAi, QIAGEN GmbH, Qiagen Str. 1, Hilden, 40724, Germany

    Christoph Erbacher

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both authors contributed equally to this review.

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Sizovs, A., McLendon, P.M., Srinivasachari, S., Reineke, T.M. (2010). Carbohydrate Polymers for Nonviral Nucleic Acid Delivery. In: Bielke, W., Erbacher, C. (eds) Nucleic Acid Transfection. Topics in Current Chemistry, vol 296. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2010_68

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