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Molecular Dynamics Simulations of Polyplexes and Lipoplexes Employed in Gene Delivery

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Intracellular Delivery II

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

Abstract

Gene therapy is an important therapeutic strategy in the treatment of a wide range of genetic disorders. Delivery of genetic materials into patient cells is limited since nucleic acids are vulnerable to degradation in extra- and intra-cellular environments. Design of delivery vehicles can overcome these limitations. Polymers and lipids are effective non-viral nucleic acid carriers; they can form stable complexes with nucleic acids known as polyplexes and lipoplexes. Despite the great amount of experimental work pursued on polymer or lipid based gene delivery systems, detailed atomic level information is needed for a better understanding of the roles the polymers and lipids play during delivery. This chapter will review molecular dynamics simulations performed on polyplexes and lipoplexes at critical stages of gene delivery. Interactions between various carriers and nucleic acids during the formation of polyplexes/lipoplexes, condensation and aggregation of nucleic acids facilitated by the carriers, binding of the polyplexes/lipoplexes to cell membrane, as well as their intracellular pathway are reviewed; and the gaps in the theoretical field are highlighted.

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Abbreviations

RNAi :

RNA interference

dsRNA:

Double stranded RNA

RISC:

RNA-induced silencing complex

siRNA :

Short interfering RNA

DOPC:

1,2-Dioleoyl-sn-glycero-3-phosphocholine

DOPE:

Dioleoylphosphatidylethanolamine

DOTAP:

1,2-Dioleoyl-3-trimethylammonium-propane

DMTAP:

Dimyristoyltrimethylammonium propane

DMPC:

Dimyristoylphosphatidylcholine

DPPC:

Dipalmitoylphosphatidylcholine

PAMAM:

Polyamidoamine

PBAE:

Poly(beta-amino ester)

PEI:

Polyethylenimine

PLL:

Poly-L-lysine

CDP:

Cyclodextrin-polycation

CME:

Clathrin-mediated endocytosis

CvME:

Caveolae/raft-mediated endocytosis

EGF:

Epidermal growth factor

MD:

Molecular dynamics

MM:

Molecular mechanics

QM:

Quantum mechanics

PME:

Particle mesh Ewald

PBC:

Periodic boundary conditions

DPD:

Dissipative particle dynamics

US:

Umbrella sampling

WHAM:

Weighted histogram analysis method

DFT:

Density functional theory

CG:

Coarse-graining

PTI:

Pancreatic trypsin inhibitor

ENM:

Elastic network model

LJ:

Lennard-Jones

MM-PBSA:

Molecular mechanic/Poisson–Boltzmann surface area

DAP:

1,3-Diaminopropane

DAPMA:

N,N-Di-(3-aminopropyl)-N-(methyl)amine

TAP:

Trimethylammonium

MC:

Monte Carlo

PMF:

Potential of mean force

CA:

Caprylic acid

LA:

Linoleic acid

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Authors and Affiliations

  1. Department of Biomedical Engineering, Faculty of Medicine and Dentistry and Engineering, University of Alberta, Edmonton, AB, Canada

    Deniz Meneksedag-Erol & Hasan Uludag

  2. Department of Mechanical Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB, Canada

    Chongbo Sun & Tian Tang

  3. Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB, Canada

    Hasan Uludag

  4. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada

    Hasan Uludag

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  1. Deniz Meneksedag-Erol
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  2. Chongbo Sun
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  3. Tian Tang
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  4. Hasan Uludag
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Correspondence to Hasan Uludag .

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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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Meneksedag-Erol, D., Sun, C., Tang, T., Uludag, H. (2014). Molecular Dynamics Simulations of Polyplexes and Lipoplexes Employed in Gene 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_15

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