Gene Delivery in Bone Tissue Engineering: Progress and Prospects Using Viral and Nonviral Strategies

Partridge, Kris; Oreffo, Richard O.C.

doi:10.1089/107632704322791934

Cited by 97 publications

(88 citation statements)

References 75 publications

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“…[8][9][10]40 The most powerful and easiest vector administration would be percutaneous in vivo injection of adenoviruses, but disadvantages, including lack of control over the target cell population and risks associated with direct viral inoculation, suggest development of other methods. rAAV has advantages over other viral and nonviral gene therapies, such as a lower potential of adverse events and higher efficiency, respectively, [18][19][20] but requires refinement for clinical usage as delivery systems.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Biological activation of bone‐related biomaterials by recombinant adeno‐associated virus vector

Nasu

Ito

Tsutsumi

et al. 2009

Journal Orthopaedic Research

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Gene therapy is a promising clinical tool that is no longer limited as a method to supplement genetic deficits, but rather is considered reliable for delivering proteins to specific tissues or cells. Recombinant adeno-associated virus (rAAV) vector is one of the most potent gene transfer vehicles. Many biomaterials have been used in reconstructive surgery, but their biological inactivity has limited their use. To overcome shortcomings of available bone-related biomaterials, we investigated the combination of rAAV with biomaterials. Taking advantage of the method of lyophilizing rAAV onto biomaterials, we showed that an rAAV coating successfully induced b-galactosidase protein expression by rat fibroblasts on hydroxyapatite, b-tricalcium phosphate, and titanium alloy in vitro. b-Galactosidase expression was detected for 8 weeks after implantation of rAAV-coated hydroxyapatite into rat back muscles in vivo. A coating of bone morphogenetic protein-2-expressing rAAV induced significant de novo bone formation on hydroxyapatite in rat back muscles. Our study demonstrates that the combination of lyophilized rAAV and biomaterials presents a promising strategy for bone regenerative medicine. ß

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Section: Discussionmentioning

confidence: 99%

“…Recombinant viral vectors are particularly effective. [8][9][10] However, combining viral vectors with biomaterials has not been fully explored. One of the most promising delivery methods incorporates viral vectors in a polymer matrix with release controlled by polymer degradation.…”

mentioning

confidence: 99%

Biological activation of bone‐related biomaterials by recombinant adeno‐associated virus vector

Nasu

Ito

Tsutsumi

et al. 2009

Journal Orthopaedic Research

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“…These vectors, however, elicit an immune response and have a limited duration of expression. 4,26 New generations of vectors have been generated to address these limitations. Among these, adeno-associated viruses appear promising as they do not encode for inflammatory viral proteins 26,[42][43][44] and have successfully been applied to stimulate osteogenesis in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3] So far, the most efficient and commonly used vectors for gene delivery have been viruses. 4 Viral vectors have been administered to skeletal sites in animals, mainly by local injections in vasculature trunks, 5 muscle, [6][7][8][9] natural cavities (e.g. joints and synovial spaces) [10][11][12][13][14] and in postsurgical, traumatic or congenital areas of bone defects.…”

Section: Introductionmentioning

confidence: 99%

Local gene transfer to calcified tissue cells using prolonged infusion of a lentiviral vector

et al. 2006

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Gene transfer using viral vectors offers the potential for the sustained expression of proteins in specific target tissues. However, in the case of calcified tissues, in vivo delivery remains problematic because of limited accessibility. The aim of this study was to test the efficiency of lentiviral vectors (LVs) on osteogenic cells in vitro, and determine the feasibility of directly transducing resident bone cells in vivo. LVs encoding for green fluorescent protein (GFP) and ameloblastin (AMBN), a protein associated with mineralization not reported in bone, were generated. The transduction efficiency of the LVs was evaluated using the MC3T3 cell line and primary calvaria-derived osteogenic cells. For in vivo delivery, the LVs were infused using osmotic minipumps through holes created in the bone of the rat hemimandible and tibia. The production of GFP and AMBN in vitro and in vivo was monitored using fluorescence microscopy. Both transgenes were expressed in MC3T3 and primary osteogenic cells. In vivo, GFP was detected at the infusion site and fibroblast-like cells, osteoblasts, osteocytes and osteoclasts expressed AMBN. Our data demonstrate, for the first time, that primary osteogenic cells are efficiently transduced with LVs and that their infusion is advantageous for locally delivering DNA to bone cells.

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“…Recently, there has been widespread concern over gene therapy because plasmid DNA could be introduced into cells of patients in gene therapy, to express the pharmaceutical proteins [1,2]. Gene therapy provides remarkable potential for the treatment of many genetic and non-genetic disorders, but the clinical application of this technology is severely hindered by the lack of an efficient and safe gene delivery system [3,4].…”

Section: Introductionmentioning

confidence: 99%

Polycationic graft copolymers of poly(N-vinylpyrrolidone) as non-viral vectors for gene transfection

Liu¹,

Cao²,

Dao-feng³

et al. 2009

Open Chemistry

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Novel graft copolymers of 2-(dimethylamino)ethyl methacrylate (DMAEMA) with N-vinylpyrrolidone (NVP) were designed and synthesized by the free radical copolymerization of DMAEMA with precursor polymers of vinyl-functionalized poly(N-vinylpyrrolidone) (PVP). The ability of the PVP-grafted copolymers to bind and condense DNA was confirmed by ethidium bromide displacement assay, agarose gel electrophoresis and transmission electron microscopy. The presence of PVP in the copolymers had a favorable effect on the biophysical properties of polymer/DNA complexes. Colloidal stable complexes obtained from the copolymer systems, were shown to be separate, uniformly spherical nanoparticles by transmission electron microscopy. The approximate diameter of the complexes was 150 -200 nm, as determined by dynamic light scattering studies. These results confirm an important role played by the PVP grafts in producing compact stable DNA complexes. The ζ-potential measurements revealed that the incorporation of the PVP grafts reduced the positive surface charge of polymer/DNA complexes. The cytotoxicity of the copolymers decreased with an increasing fraction of PVP. Furthermore, in vitro transfection experiments with these copolymers showed improved ability of transfection in cell culture, demonstrating an important role for PVP grafts in enhancement of the transfection efficiency.© Versita Warsaw and Springer-Verlag Berlin Heidelberg.

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Gene Delivery in Bone Tissue Engineering: Progress and Prospects Using Viral and Nonviral Strategies

Cited by 97 publications

References 75 publications

Biological activation of bone‐related biomaterials by recombinant adeno‐associated virus vector

Biological activation of bone‐related biomaterials by recombinant adeno‐associated virus vector

Local gene transfer to calcified tissue cells using prolonged infusion of a lentiviral vector

Polycationic graft copolymers of poly(N-vinylpyrrolidone) as non-viral vectors for gene transfection

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