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Conference Paper: A novel aptamer-mediated approach for degenerative disc disease therapy
Title | A novel aptamer-mediated approach for degenerative disc disease therapy |
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Authors | |
Issue Date | 2013 |
Citation | The 9th Pan Pacific Connective Tissue Societies Symposium (PPCTSS 2013), Hong Kong, China, 24-27 November 2013. In Program Book, 2013, abstract no. 0053 How to Cite? |
Abstract | The intervertebral disc is responsible for absorbing shock and transmitting load, allowing the spine to
bend and move. Disc degeneration may cause serious low back pain and affect daily life. Aggrecanases
ADAMTS-4 and -5 are critical proteins involved in the development of degenerative disc disease
(DDD) and osteoarthritis. They have been used as targets for inhibitor selection against DDD in recent
studies both in vitro and in silico. Small molecules targeting the catalytic domain of aggrecanases have
been developed but have broad inhibitory activity which cause serious side effects. Nucleic acid
aptamers can potentially solve this problem. Aptamers are short, single-stranded oligonucleotides,
which bind to their targets through 3D conformational complementarity. Aptamers are frequently
called ‘chemical antibodies’ because of their high specificity and affinity. More than 20 aptamers for
the treatment of various diseases are evaluated in clinical trials. Recent studies on aggrecanases have
also been restrained by the low expression level and low solubility of the catalytic domain. Our studies
have developed new ways to express, refold and purify human ADAMTS-4 and ADAMTS-5.
Catalytic domain incorporating both the disintegrin domain and thrombospondin motif were expressed
and purified from E. coli with high yield for the first time. Specific aptamers are being selected against
each aggrecanase through a process called Systematic Evolution of Ligands by Exponential
enrichment (SELEX). Selected aptamers will then be characterized and evaluated as a foundation for
further DDD therapeutic development. |
Description | Conference Theme: The Extracellular Matrix Niche Poster Presentation |
Persistent Identifier | http://hdl.handle.net/10722/203817 |
DC Field | Value | Language |
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dc.contributor.author | Yu, Y | en_US |
dc.contributor.author | Tanner, JA | en_US |
dc.date.accessioned | 2014-09-19T16:41:12Z | - |
dc.date.available | 2014-09-19T16:41:12Z | - |
dc.date.issued | 2013 | en_US |
dc.identifier.citation | The 9th Pan Pacific Connective Tissue Societies Symposium (PPCTSS 2013), Hong Kong, China, 24-27 November 2013. In Program Book, 2013, abstract no. 0053 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/203817 | - |
dc.description | Conference Theme: The Extracellular Matrix Niche | - |
dc.description | Poster Presentation | - |
dc.description.abstract | The intervertebral disc is responsible for absorbing shock and transmitting load, allowing the spine to bend and move. Disc degeneration may cause serious low back pain and affect daily life. Aggrecanases ADAMTS-4 and -5 are critical proteins involved in the development of degenerative disc disease (DDD) and osteoarthritis. They have been used as targets for inhibitor selection against DDD in recent studies both in vitro and in silico. Small molecules targeting the catalytic domain of aggrecanases have been developed but have broad inhibitory activity which cause serious side effects. Nucleic acid aptamers can potentially solve this problem. Aptamers are short, single-stranded oligonucleotides, which bind to their targets through 3D conformational complementarity. Aptamers are frequently called ‘chemical antibodies’ because of their high specificity and affinity. More than 20 aptamers for the treatment of various diseases are evaluated in clinical trials. Recent studies on aggrecanases have also been restrained by the low expression level and low solubility of the catalytic domain. Our studies have developed new ways to express, refold and purify human ADAMTS-4 and ADAMTS-5. Catalytic domain incorporating both the disintegrin domain and thrombospondin motif were expressed and purified from E. coli with high yield for the first time. Specific aptamers are being selected against each aggrecanase through a process called Systematic Evolution of Ligands by Exponential enrichment (SELEX). Selected aptamers will then be characterized and evaluated as a foundation for further DDD therapeutic development. | - |
dc.language | eng | en_US |
dc.relation.ispartof | Pan Pacific Connective Tissue Societies Symposium, PPCTSS 2013 | en_US |
dc.title | A novel aptamer-mediated approach for degenerative disc disease therapy | en_US |
dc.type | Conference_Paper | en_US |
dc.identifier.email | Tanner, JA: jatanner@hku.hk | en_US |
dc.identifier.authority | Tanner, JA=rp00495 | en_US |
dc.identifier.hkuros | 238504 | en_US |