Gene Therapy in Orthopaedic Surgery

Hannallah, David; Peterson, Brett; Lieberman, Jay R.; Fu, Freddie H.; Huard, Johnny

doi:10.2106/00004623-200206000-00023

Cited by 53 publications

(45 citation statements)

References 201 publications

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“…They have extremely high transduction efficiencies and can accommodate large cDNA fragments. 7 Cell transduction is feasible in most cell types, and thus adenovirus can be broadly used to transduce different tissues. The inability to integrate into the host genome ensures that transgene expression is transient, which is preferable for bone healing because continued gene expression following complete defect regeneration is unnecessary and possibly pathogenic.…”

Section: Discussionmentioning

confidence: 99%

“…Compared to nonviral vectors, viral vectors exhibit much greater transduction efficiency. 7 In an ex vivo gene therapy approach, cells are collected, transduced and cultured in vitro before in vivo implantation. 8 Although the majority of virus particles can be excluded before transplantation to avoid risk systemic infection, harvesting and culturing cells from patients may render this approach impractical for many applications.…”

Section: Introductionmentioning

confidence: 99%

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Localized viral vector delivery to enhance in situ regenerative gene therapy

Wang

Hollister

et al. 2007

Gene Ther

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A lyophilization method was developed to locally release adenoviral vectors directly from biomaterials for in situ regenerative gene therapy. Adenovirus expressing a b-galactosidase reporter gene (AdLacZ) was mixed with different excipient formulations and lyophilized on hydroxyapatite (HA) disks followed by fibroblasts culturing and 5-bromo-4-chloro-3-indolyl-b-D-galactopyranoside (X-gal) staining, suggesting 1 M sucrose in phosphate-buffered saline had best viability. Adenovirus release studies showed that greater than 30% virus remained on the material surface up to 16 h. Lyophilized adenovirus could be precisely localized in defined patterns and the transduction efficiency was also improved. To determine if the lyophilization formulations could preserve viral bioactivity, the lyophilized AdLacZ was tested after being stored at varying temperatures. Bioactivity of adenovirus lyophilized on HA was maintained for greater than 6 months when stored at À801C. In vivo studies were performed using an adenovirus encoding BMP-2 (AdBMP-2). AdBMP-2 was lyophilized in gelatin sponges and placed into rat critical-size calvarial defects for 5 weeks. Micro-computed tomography (m-CT) analysis demonstrated that free-form delivery of AdBMP-2 had only modest effects on bone formation. In contrast, AdBMP-2 lyophilized in gelatin sponges led to more than 80% regeneration of critical-size calvarial defects. Gene Therapy (2007) 14, 891-901.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Localized viral vector delivery to enhance in situ regenerative gene therapy

Wang

Hollister

et al. 2007

Gene Ther

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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%

“…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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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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“…2) Cell-based therapy: involves direct contribution to tissue regeneration, genetic modification of cells to act as vehicles for gene therapy and differentiation into various tissue types [18] .…”

Section: Scaffoldmentioning

confidence: 99%

Tissue Engineering: Emerging Concept in Oral Maxillofacial Reconstruction-A Review Article

Kumar¹

2017

JMSCR

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Gene Therapy in Orthopaedic Surgery

Cited by 53 publications

References 201 publications

Localized viral vector delivery to enhance in situ regenerative gene therapy

Localized viral vector delivery to enhance in situ regenerative gene therapy

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

Tissue Engineering: Emerging Concept in Oral Maxillofacial Reconstruction-A Review Article

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