Barriers to Non-viral Vector-mediated Gene Delivery in the Nervous System

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2011 Jan 13

PMID 21225319

Citations 58

Authors

Francisco C Perez-Martinez

Javier Guerra

Inmaculada Posadas

Valentin Cena

Affiliations

Soon will be listed here.

Abstract

Efficient methods for cell line transfection are well described, but, for primary neurons, a high-yield method different from those relying on viral vectors is lacking. Viral transfection has several drawbacks, such as the complexity of vector preparation, safety concerns, and the generation of immune and inflammatory responses when used in vivo. However, one of the main problems for the use of non-viral gene vectors for neuronal transfection is their low efficiency when compared with viral vectors. Transgene expression, or siRNA delivery mediated by non-viral vectors, is the result of multiple processes related to cellular membrane crossing, intracellular traffic, and/or nuclear delivery of the genetic material cargo. This review will deal with the barriers that different nanoparticles (cationic lipids, polyethyleneimine, dendrimers and carbon nanotubes) must overcome to efficiently deliver their cargo to central nervous system cells, including internalization into the neurons, interaction with intracellular organelles such as lysosomes, and transport across the nuclear membrane of the neuron in the case of DNA transfection. Furthermore, when used in vivo, the nanoparticles should efficiently cross the blood-brain barrier to reach the target cells in the brain.

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References

Vasir J, Labhasetwar V . Biodegradable nanoparticles for cytosolic delivery of therapeutics. Adv Drug Deliv Rev. 2007; 59(8):718-28. PMC: 2002520. DOI: 10.1016/j.addr.2007.06.003. View

Mukherjee S, Ghosh R, Maxfield F . Endocytosis. Physiol Rev. 1997; 77(3):759-803. DOI: 10.1152/physrev.1997.77.3.759. View

Binder H, Lindblom G . Charge-dependent translocation of the Trojan peptide penetratin across lipid membranes. Biophys J. 2003; 85(2):982-95. PMC: 1303219. DOI: 10.1016/S0006-3495(03)74537-8. View

Posadas I, Guerra F, Cena V . Nonviral vectors for the delivery of small interfering RNAs to the CNS. Nanomedicine (Lond). 2010; 5(8):1219-36. DOI: 10.2217/nnm.10.105. View

Ma K, Hu M, Qi Y, Qiu L, Jin Y, Yu J . Structure-transfection activity relationships with glucocorticoid-polyethyl-enimine conjugate nuclear gene delivery systems. Biomaterials. 2009; 30(22):3780-9. DOI: 10.1016/j.biomaterials.2009.03.042. View

Pardridge W, Triguero D, Buciak J, Yang J . Evaluation of cationized rat albumin as a potential blood-brain barrier drug transport vector. J Pharmacol Exp Ther. 1990; 255(2):893-9. View

Gregoriadis G . Liposomes in the therapy of lysosomal storage diseases. Nature. 1978; 275(5682):695-6. DOI: 10.1038/275695a0. View

Mayor S, Pagano R . Pathways of clathrin-independent endocytosis. Nat Rev Mol Cell Biol. 2007; 8(8):603-12. PMC: 7617177. DOI: 10.1038/nrm2216. View

Branden L, Mohamed A, Smith C . A peptide nucleic acid-nuclear localization signal fusion that mediates nuclear transport of DNA. Nat Biotechnol. 1999; 17(8):784-7. DOI: 10.1038/11726. View

10.

Kostarelos K, Bianco A, Prato M . Promises, facts and challenges for carbon nanotubes in imaging and therapeutics. Nat Nanotechnol. 2009; 4(10):627-33. DOI: 10.1038/nnano.2009.241. View

11.

Yang H . Nanoparticle-mediated brain-specific drug delivery, imaging, and diagnosis. Pharm Res. 2010; 27(9):1759-71. PMC: 2933363. DOI: 10.1007/s11095-010-0141-7. View

12.

Creusat G, Rinaldi A, Weiss E, Elbaghdadi R, Remy J, Mulherkar R . Proton sponge trick for pH-sensitive disassembly of polyethylenimine-based siRNA delivery systems. Bioconjug Chem. 2010; 21(5):994-1002. DOI: 10.1021/bc100010k. View

13.

Liu Y, Huang R, Han L, Ke W, Shao K, Ye L . Brain-targeting gene delivery and cellular internalization mechanisms for modified rabies virus glycoprotein RVG29 nanoparticles. Biomaterials. 2009; 30(25):4195-202. DOI: 10.1016/j.biomaterials.2009.02.051. View

14.

Weigel P, Oka J . Temperature dependence of endocytosis mediated by the asialoglycoprotein receptor in isolated rat hepatocytes. Evidence for two potentially rate-limiting steps. J Biol Chem. 1981; 256(6):2615-7. View

15.

Guerra-Crespo M, Charli J, Rosales-Garcia V, Pedraza-Alva G, Perez-Martinez L . Polyethylenimine improves the transfection efficiency of primary cultures of post-mitotic rat fetal hypothalamic neurons. J Neurosci Methods. 2003; 127(2):179-92. DOI: 10.1016/s0165-0270(03)00125-0. View

16.

Zabner J, Fasbender A, Moninger T, Poellinger K, Welsh M . Cellular and molecular barriers to gene transfer by a cationic lipid. J Biol Chem. 1995; 270(32):18997-9007. DOI: 10.1074/jbc.270.32.18997. View

17.

Kim J, Choi J, Nam K, Lee M, Park J, Lee J . Enhanced transfection of primary cortical cultures using arginine-grafted PAMAM dendrimer, PAMAM-Arg. J Control Release. 2006; 114(1):110-7. DOI: 10.1016/j.jconrel.2006.05.011. View

18.

Kannan S, Kolhe P, Raykova V, Glibatec M, Kannan R, Lieh-Lai M . Dynamics of cellular entry and drug delivery by dendritic polymers into human lung epithelial carcinoma cells. J Biomater Sci Polym Ed. 2004; 15(3):311-30. DOI: 10.1163/156856204322977201. View

19.

Kim I, Lim C, Kim J, Nam H, Nam K, Kim S . Neuroprotection by biodegradable PAMAM ester (e-PAM-R)-mediated HMGB1 siRNA delivery in primary cortical cultures and in the postischemic brain. J Control Release. 2009; 142(3):422-30. DOI: 10.1016/j.jconrel.2009.11.011. View

20.

Bruckner K, Pablo Labrador J, Scheiffele P, Herb A, Seeburg P, Klein R . EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft membrane microdomains. Neuron. 1999; 22(3):511-24. DOI: 10.1016/s0896-6273(00)80706-0. View