Gene delivery

The initial approach to gene therapy involved manipulation of gene expression ex vivo. Toward this end, the desired target cells are identified and subsequently removed from the subject, transfected in vitro, then reintroduced into the patient. A number of protocols have been established for the ex vivo transfection of a wide variety of cell types. This method allows specific cell targeting and high transfection efficiency. However, the process is time consuming, complex, and costly. Additionally, the method is not applicable to all situations, such as those in which an immediate modification is required. 

Alternatively, gene therapy can be performed through in vivo manipulation of gene expression. In this case, the desired genes must be directly delivered to the appropriate cell population in the subject in vivo. This strategy offers several advantages over the ex vivo approach. For instance, 

These studies provide the groundwork for the use of ORMOSIL nanoparticle formulations for in vivo gene transfer into the central nervous system, and demonstrate that ORMOSIL nanoparticles can potentially provide a safe and efficient mechanism for in vivo gene therapy. The results of this nanomedicine approach 

Radiotherapeutics attack cancer by causing radiation damage to DNA in cells. The requirements differ from those for drug delivery because the radiotherapeutic can act at a distance and does not have to separate from the delivery particle. Radiotherapeutics can be selected to provide action over a range of distances, from tens of nanometers to hundreds of microns. Three radiotherapy modalities can be identified. Brachytherapy, most often used with beta-emitters, uses tightly enclosed radioactive material that is brought in close proximity to the tumor. A second modality is intravenous injection so that the radiopharmaceutical binds to the outside of the tumor cells or is taken up by the cell and irradiates from within. The third approach uses a carrier loaded with the radiotherapeutic that is transported to the vicinity of the target cells, and then released. 

Although magnetic separation is used extensively in the laboratory for diagnostic purposes, its use in vivo faces the same problems as encountered by magnetic drug delivery, namely the shallow penetration of the magnetic fidd. Nonetheless, magnetic separation is currently considered to show much promise in the treatment of soft forms of cancer (e.g., leukemia) that are the most difficult to cure [260]. 

DNA CnVD CniO CnUD CMO CntfD CnVD Cr D CnVD CnVD CntfD CnVD CnVD CnVD Cnt/D CnVD CnVD Cr4fD 

Qin et al also modified MWNTs with polyamidoamine (PAMAM) to increase the CNTs gene loading, and eventually to improve the transfection performance of CNTs. However, though the MWNT-PAMAM hybrid could deliver the GFP gene into cultured HeLa cells more efficiently than the unmodified CNTs, the efficiency was much lower than Lipofectamine 2000. The surfaces of SWNTs were also functionalized with cationic glycopolymers, and the copolymer modified SWNTs were found to be biocompatible and exhibit transfection efficiencies that are comparable to the commercially available agent Lipofectamine 2000. Various modified CNTs were tested in different cell lines for gene delivery.  

In contrast to the above well-known strategies to modify CNTs for DNA delivery, Geyik et al recently developed a new approach using the covalent attachment of linearized plasmid DNA to MWNTs. Cifuentes-Rius et al demonstrated that two different monomers, pentafluorophenyl methacrylate (PFM) and allylamine (AA), could be polymerized on the CNT surface in a home-built plasma reactor, allowing the formation of CNT-mediated gene delivery vectors.  

Except for the polymerization modification, CNTs were also fabricated with other materials, such as metals. A new strategy to deliver exogenous pDNA was also developed with CNT that contain Ni particles enclosed in their tips. Because of the presence of nickel, the complexes have some extra properties that can be used. It was shown that the gene expression was 80-100% of the cell 

The ability of GO to strongly bind to ssDNA yet without a strong interaction with dsDNA molecules has been extensively applied in the gene delivery. Liu et al. pioneered gene delivery by GO in 2011. They employed GO bound with eationic polymers, PEI with two different molecular weights at 1.2 kDa and 10 kDa, forming GO-PEI-1.2k and GO-PEG-lOk complexes as non-toxic 

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Kost, T. A., and Condreay, J. P. (2002). Recombinant baculovirases as mammalian cell gene-delivery vectors. Trends Biotechnol. 20 173—180. 

Zhao Z and Eong LKW. Polyphosphoestes in drug and gene delivery. Adv Drug Deliv Rev, 2003, 55, 483 99. 

Davis, M.E., Non-viral gene delivery systems. Curr. Opin. Biotechnol. 2002, 13, 128-131. 

Green JJ, Langer R, Anderson DG (2008) A combinatorial polymer library approach yields insight into nonviral gene delivery. Acc Chem Res 41 749-759... 

DD Lasic. Liposomes in Gene Delivery. Boca Raton, FL CRC Press, 1997. 

AV Kabanov, FC Szoka Jr, LW Seymour. In PF AV Kabanov, LW Seymour, eds. Interpoly-electrolyte Complexes for Gene Delivery Polymer Aspects of Transfection Activity. Chichester, UK Wiley, 1998, pp 197-218. 

Adamantane has also been used for lipidic nucleic acid synthesis as a hydrophobic group. Two major problems in gene delivery are the low uptake of... 

The final part, on pharmaceutical applications, consists of five chapters and includes topics such as drugs at liquid interfaces, NMR studies, and drugs and gene delivery. 

Lipid Bilayers in Cells Implications in Drug and Gene Delivery T. Marjukka Suhonen, Pekka Suhonen, and Arto Urtti... 

Lipid Bilayers in Cells Implications in Drug and Gene Delivery... 

Pharmaceutical Gene Delivery Systems, edited by Alain Rolland and Sean M. Sullivan... 

Polymers as Drugs, Conjugates and Gene Delivery Systems... 

Trepel M, Grifman M, Weitzman MD et al. Molecular adaptors for vascular-targeted adenoviral gene delivery. Hum Gene Ther 2000 11 1971-1981. 

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