The encapsulation of ribozymes in biodegradable polymeric matrices

Jackson, John K.; Liang, Linda S.; Hunter, William L.; Reynolds, Mark A.; Sandberg, Jennifer A.; Springate, Chris; Burt, Helen M.

doi:10.1016/s0378-5173(02)00228-4

Cited by 27 publications

(15 citation statements)

References 23 publications

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“…Molecular delivery systems, such as liposomes or polymeric paste formulations, have been used to provide highly efficient transfection of oligonucleotides. 42,43 In conclusion, the results presented here provide the first evidence that gene targeting by ribozymes modulates arthritis in vivo. We show that systemic delivery of plasmid-based ribozymes targeting TNF-a mRNA has a substantial therapeutic effect on arthritis and joint destruction in mice, proving that nonviral gene therapy vectors can be successfully used for in vivo treatments without inducing immune responses.…”

Section: Ribozyme Targeting Tnf-a Inhibits Autoimmune Arthritis R Kumsupporting

confidence: 52%

Gene targeting by ribozyme against TNF-α mRNA inhibits autoimmune arthritis

Kumar

Dammai²,

Yadava³

et al. 2005

Gene Ther

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Ribozymes are catalytic RNA that bind and cleave specific regions of target RNA. Therefore, protein synthesis by the target RNA may be specifically inhibited by ribozymes. In this study, we have investigated if ribozymes possess therapeutic activity on inflammatory processes in vivo, as judged from effects on an arthritis model. A hammerhead ribozyme against TNF-a was designed and its catalytic activity in vitro was verified. The ribozyme was employed in vivo without any delivery system, as the plasmid-based ribozyme was taken up adequately by various tissues in mice by intravenous injection. The ability of the ribozyme to regulate the development of collagen-induced arthritis (CIA), a model largely dependent on TNF-a, was investigated. Systemic administration of the ribozyme to mice immunized with collagen type II in CFA significantly reduced the development of CIA. No effect was observed with a catalytically inactive variant of the ribozyme. Furthermore, the ribozyme efficiently blocked cartilage and bone destruction in the joints and ameliorated established CIA. These data demonstrate for the first time that gene targeting by a ribozyme to inactivate TNF-a in vivo is highly efficient in suppressing autoimmune arthritis, thus providing proof of concept that it may be used as therapeutic tool for TNF-a-dependent chronic inflammatory disorders.

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Section: Ribozyme Targeting Tnf-a Inhibits Autoimmune Arthritis R Kumsupporting

confidence: 52%

Gene targeting by ribozyme against TNF-α mRNA inhibits autoimmune arthritis

Kumar

Dammai²,

Yadava³

et al. 2005

Gene Ther

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“…Unfortunately, most of the commercially available cationic lipids are unstable in serum therefore most of "in vivo" administrations use alternative tools such as polymeric matrices [Aigner A. et al (2002)], dendrimers [Yoo H., Juliano R.L., (2000)], nanospheres and biodegradable polymers [Putney S.D. et al (1999), Jackson et al (2002)], receptor ligands or antibodies [Biessen E. et al (1999)] and peptidic carriers [Morris M.C. et Al (1997) …”

Section: B) Carriers To Improve Cell Uptakementioning

confidence: 99%

Synthetic Hammerhead Ribozymes as Therapeutic Tools to Control Disease Genes

Citti¹,

Rainaldi²

2005

CGT

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Ribozymes are RNA molecules that have the ability to catalyse the cleavage and formation of covalent bonds in RNA strands at specific sites. The "hammerhead" motif, approximately 30-nucleotide long, is the smallest endonucleolytic cis-acting ribozyme structure found in natural circular RNAs of some plant viroids. Hammerhead ribozymes became appealing when it was shown that it is possible to produce trans-acting ribozymes directed against RNA sequences of interest. Since then, gene-tailored ribozymes have been designed, produced and given to cells to knock down the expression of specific genes. At present, this technology has advanced so much that many hammerhead ribozymes are being used in clinical trials. With this work we would provide some guidelines to design efficient trans-acting hammerhead ribozymes as well as review the recent results obtained with them as gene therapy tools.

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“…After the first 15 days of keeping the microparticles in aqueous solution, the enzymatic activity was maintained at (70.4 ± 3.2)% of the initial value showing an abrupt decrease at the third week. This behavior could represent an advantage if the microparticles were employed for the treatment of enzymatic diseases, in which prolonged therapeutic activity along the time is required to enhance the patient's quality of life 11–22…”

Section: Resultsmentioning

confidence: 99%

Enzymatic biodegradable micro‐reactors for therapeutic applications

2007

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Poly(epsilon-caprolactone) is a well known biocompatible polymer, widely used as drug immobilization systems. In this work poly(epsilon-caprolactone) microparticles with average size between 5 and 25 microm have been prepared by O/W emulsion evaporation method. Inside the microparticles, we have encapsulated Glucose Oxidase with the aim of preparing micro-reactors for enzymatic therapy. These microparticles were structurally characterized and its enzymatic activity analyzed in order to improve the enzyme entrapment. Thus, at the optimum synthesis conditions the enzyme entrapped in the microparticles showed an enzymatic activity of (29.9 +/- 2.1)% comparing with the same amount of free enzyme. Moreover the microparticles maintained a (70.4 +/- 3.2)% of their initial enzymatic activity after placing them in buffer solution for two weeks.

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The encapsulation of ribozymes in biodegradable polymeric matrices

Cited by 27 publications

References 23 publications

Gene targeting by ribozyme against TNF-α mRNA inhibits autoimmune arthritis

Gene targeting by ribozyme against TNF-α mRNA inhibits autoimmune arthritis

Synthetic Hammerhead Ribozymes as Therapeutic Tools to Control Disease Genes

Enzymatic biodegradable micro‐reactors for therapeutic applications

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