Aggregation of Synthetic Gene Delivery Vectors Enhance the Cellular Association and Uptake for in vitro Transfection

Development of safe and efficient synthetic gene delivery vectors is hampered with limited understanding the fundamental correlation of physicochemical properties of the vectors with their biological activities. Five major barriers contributing to poor transfection efficiency of synthetic vectors in...

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Main Authors: Simeon, Fritz, Tam, Michael K.C., Hatton, T. Alan, Too, Heng-Phon
Format: Article
Language:English
Published: 2007
Subjects:
Online Access:http://hdl.handle.net/1721.1/35871
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author Simeon, Fritz
Tam, Michael K.C.
Hatton, T. Alan
Too, Heng-Phon
author_facet Simeon, Fritz
Tam, Michael K.C.
Hatton, T. Alan
Too, Heng-Phon
author_sort Simeon, Fritz
collection MIT
description Development of safe and efficient synthetic gene delivery vectors is hampered with limited understanding the fundamental correlation of physicochemical properties of the vectors with their biological activities. Five major barriers contributing to poor transfection efficiency of synthetic vectors include cellular association, endosomal escape, intracellular trafficking, nuclear translocation and transcription of exogenous genes. In this study, the correlation of physicochemical properties of polymer-based synthetic gene delivery vectors (polyplexes) with cellular association as the first barrier for in vitro transfection was investigated. Polyethylene oxide block copolymer with poly(2-(dimethylamino)ethyl methacryate) (PEO-b-pDMAEMA) was chosen as the model in this study. Cellular association and transfection efficiency of block copolymer complexes were studied in Neuro2A cells. Quantitative real time polymerase chain reaction (PCR) was applied to elucidate the cellular association of polyplexes. Physicochemical properties of the vectors including size and surface charge were characterized using light scattering measurements. Formation of aggregate was found as the major indication for high cellular association and uptake for in vitro transfection.
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spelling mit-1721.1/358712019-04-10T09:58:51Z Aggregation of Synthetic Gene Delivery Vectors Enhance the Cellular Association and Uptake for in vitro Transfection Simeon, Fritz Tam, Michael K.C. Hatton, T. Alan Too, Heng-Phon PEO-b-pDMAEMA DLS Zeta Potential Transfection Quantitative Real Time PCR Development of safe and efficient synthetic gene delivery vectors is hampered with limited understanding the fundamental correlation of physicochemical properties of the vectors with their biological activities. Five major barriers contributing to poor transfection efficiency of synthetic vectors include cellular association, endosomal escape, intracellular trafficking, nuclear translocation and transcription of exogenous genes. In this study, the correlation of physicochemical properties of polymer-based synthetic gene delivery vectors (polyplexes) with cellular association as the first barrier for in vitro transfection was investigated. Polyethylene oxide block copolymer with poly(2-(dimethylamino)ethyl methacryate) (PEO-b-pDMAEMA) was chosen as the model in this study. Cellular association and transfection efficiency of block copolymer complexes were studied in Neuro2A cells. Quantitative real time polymerase chain reaction (PCR) was applied to elucidate the cellular association of polyplexes. Physicochemical properties of the vectors including size and surface charge were characterized using light scattering measurements. Formation of aggregate was found as the major indication for high cellular association and uptake for in vitro transfection. Singapore-MIT Alliance (SMA) 2007-02-05T23:51:52Z 2007-02-05T23:51:52Z 2007-01 Article http://hdl.handle.net/1721.1/35871 en Chemical and Pharmaceutical Engineering (CPE) application/pdf
spellingShingle PEO-b-pDMAEMA
DLS
Zeta Potential
Transfection
Quantitative Real Time PCR
Simeon, Fritz
Tam, Michael K.C.
Hatton, T. Alan
Too, Heng-Phon
Aggregation of Synthetic Gene Delivery Vectors Enhance the Cellular Association and Uptake for in vitro Transfection
title Aggregation of Synthetic Gene Delivery Vectors Enhance the Cellular Association and Uptake for in vitro Transfection
title_full Aggregation of Synthetic Gene Delivery Vectors Enhance the Cellular Association and Uptake for in vitro Transfection
title_fullStr Aggregation of Synthetic Gene Delivery Vectors Enhance the Cellular Association and Uptake for in vitro Transfection
title_full_unstemmed Aggregation of Synthetic Gene Delivery Vectors Enhance the Cellular Association and Uptake for in vitro Transfection
title_short Aggregation of Synthetic Gene Delivery Vectors Enhance the Cellular Association and Uptake for in vitro Transfection
title_sort aggregation of synthetic gene delivery vectors enhance the cellular association and uptake for in vitro transfection
topic PEO-b-pDMAEMA
DLS
Zeta Potential
Transfection
Quantitative Real Time PCR
url http://hdl.handle.net/1721.1/35871
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