Biological potency of microsphere encapsulated plasmid DNA

Hao, Tang; McKeever, Una; Hedley, Mary Lynne

doi:10.1016/s0168-3659(00)00304-7

Cited by 26 publications

(18 citation statements)

References 15 publications

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“…Polyplexes kept at 4°C retained their transfection efficiency during 1 year of storage. This is in accordance with other long-term storage studies of DNA complexes (12,19) and it is even suggested that plasmid DNA will remain stable for 2 years at 5°C assuming that depurination and ␤-elimination are the only degrading mechanisms occurring (13). Chitosan-based polyplexes stored in a freeze-dried condition at 4°C also retain their properties when subjected for long-term storage (8,11).…”

Section: Discussionsupporting

confidence: 90%

“…It is previously shown that a change in the chemical structure of plasmid DNA not necessarily is detected as a change in the biologic activity (12). In order to better compare biologic and analytical assays it is necessary to develop quantitative measures of structural stability that do not rely on dye intercalation, as different isoforms of DNA will also produce different levels of staining with for instance the indicator dye ethidium bromide (12).…”

Section: Discussionmentioning

confidence: 99%

“…Naked plasmids exist in three major tertiary structures: i) supercoiled representing the most compact stable isomer, ii) open circle occurring when there are breaks in the phosphate backbone of the double-stranded molecule, and iii) linear, indicating breaks at a single site in both strands of the circular plasmid (12,13). Degradation of DNA in aqueous environment are mainly caused by hydrolysis (depurination and ␤-elimination reactions) and oxidation (via free radicals) (13,14) and a degradation of the plasmid may be seen as a change in the tertiary structure.…”

Section: Introductionmentioning

confidence: 99%

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Long-Term Stability of Chitosan-Based Polyplexes

et al. 2004

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Long-Term Stability of Chitosan-Based Polyplexes

et al. 2004

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“…There is evidence to suggest that relaxed forms of DNA are no less efficient at gene delivery than supercoiled forms. 24 Further, when Hao et al 25 analysed DNA released from PLG microspheres over 14 days, they demonstrated a gradual conversion of supercoiled plasmid to the nicked isoform but showed no consequent reduction in the biological activity of this DNA, as measured by transfection of COS-7 cells in vitro. The use of linear DNA however, resulted in markedly lower transfection efficiency, and steps to minimize sequential degradation of encapsulated DNA from nicked to linear forms may be important.…”

Section: Discussionmentioning

confidence: 99%

Poly (D, L-lactide-co-glycolide)/DNA microspheres to facilitate prolonged transgene expression in airway epithelium in vitro, ex vivo and in vivo

et al. 2003

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“…therefore, it is essential to establish an efficient and safe gene delivery protocol. nanoparticles (nps) based on plgA have been suggested as a promising carrier for DnA (7,8). In addition to its biodegradability and biocompatibility, the potential of nanoparticles as a controlled release drug delivery system and protective agent of DnA against nucleinase has attracted much attention (9,10).…”

mentioning

confidence: 99%

Efficient inhibition of ovarian cancer by short hairpin RNA targeting claudin-3

Sun

Yi²,

Song³

et al. 2011

Oncol Rep

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Abstract. ovarian cancer is one of the most lethal gynecologic neoplasms. even though various new chemotherapeutics have been developed for the treatment of ovarian cancer, drug resistance and undesired serious side effects remain unavoidable obstacles for chemotherapeutic approaches. new strategies to overcome the therapeutic dilemma are needed. claudin-3 (clDn3) is a recently discovered gene generally overexpressed in human ovarian cancers but not in normal ovarian tissue. Its high expression has been identified to associate with the invasion, proliferation and survival of cancer cells, making it a promising target for gene therapy of ovarian cancer. However, in gene therapy, traditional gene carriers such as virus or cationic liposomes suffer from distressing shortcomings of potential carcinogenicity, obvious cytotoxicity and immunogenicity. nanoparticles (nps) based on plgA are a novel gene delivery system with good biodegradability, excellent biocompatibility and low toxcity for in vivo gene delivery compared with traditional gene carriers. We constructed a plasmid expressing shrnA targeted clDn3 (pshclDn3) encapsulated with plgA-nps, and administered it by i.p. injection to nude mice bearing intraperitoneal sKoV3 ovarian cancer, to investigate the antitumor potential of knocking down clDn3. After 12 times of administration, the tumors of each group were compared. the underlying antitumor mechanisms were revealed by immunostaining of cD31, Ki-67 and tUnel assay, to exhibit possible alterations in microvessel density, cell proliferation and cell apoptosis. our study demonstrated that i.p. administration of pshclDn3 effectively suppressed the expression of clDn3 and, thus, inhibited the growth of ovarian tumors, significantly reducing tumor weight by 67.4% compared with blank controls (p<0.05). Immunostaining of cD31, Ki-67 and tUnel assay demonstrated decreased angiogenesis (p<0.05), reduced proliferation (p<0.05) and increased apoptosis (p<0.05) in the pshclDn3 treated group compared with controls. no obvious toxicity of plgA-nps was observed either in vitro or in vivo. our results indicated that knockdown of clDn3 by pshclDn3 encapsulated in plgA nps may provide a promising approach for the treatment of ovarian cancer. IntroductionOvarian cancer, which accounts for more than 50% death of gynecologic malignancy, is the most lethal gynecologic carcinoma (1). Due to its few and imperceptible early symptoms, ovarian cancer is mostly at advanced stage in most patients during the initial diagnosis. Although patients may initially respond to the combination treatment of surgical and chemical therapies, most of them will inevitably die from relapse and the development of chemotherapy-resistant recurrence (2). The overall 5-year relative survival rate is no more than 50% (3). therefore, new strategies to improve the treatment status of ovarian cancer are urgently needed.gene therapy is a novel therapeutic strategy different from traditional therapies. It exclusively targets the key gene for tumorigenesis, achieves ...

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Biological potency of microsphere encapsulated plasmid DNA

Cited by 26 publications

References 15 publications

Long-Term Stability of Chitosan-Based Polyplexes

Long-Term Stability of Chitosan-Based Polyplexes

Poly (D, L-lactide-co-glycolide)/DNA microspheres to facilitate prolonged transgene expression in airway epithelium in vitro, ex vivo and in vivo

Efficient inhibition of ovarian cancer by short hairpin RNA targeting claudin-3

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