Barbara Mui
University of British Columbia
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Featured researches published by Barbara Mui.
Molecular Membrane Biology | 1998
M. J. Hope; Barbara Mui; S. Ansell; Q. F. Ahkong
Polymeric, nucleic acid drugs must be protected from endogenous nucleases and delivered to target cell nuclei in order to maximize their activity. Constructs expressing therapeutic genes, antisense oligonucleotides and ribozymes can be delivered into cells by viral vectors, but concerns over safety and clinical utility have led to research into the development of alternative, non-viral delivery systems. Antisense and ribozyme drug development has focused upon modifications to the natural oligonucleotide chemistry which make the molecules resistant to nuclease degradation. These novel oligonucleotides cannot be generated by transgenes and must be administered in similar fashion to conventional drugs. However, oligonucleotides cannot cross membranes by passive diffusion and intracellular delivery for these drugs is very inefficient. Here we review the recent advances in forming lipid-DNA particles designed to mimic viral delivery of DNA. Most evidence now supports the hypothesis that lipid-DNA drugs enter target cells by endocytosis and disrupt the endosomal membrane, releasing nucleic acid into the cytoplasm. The mechanisms of particle formation and endosome disruption are not well understood. Cationic lipids are employed to provide an electrostatic interaction between the lipid carrier and polyanionic nucleic acids, and they are critical for efficient packaging of the drugs into a form suitable for systemic administration. However, their role in endosome disruption and other aspects of successful delivery leading to gene expression or inhibition of mRNA translation are less clear. We discuss the propensity of lipid-nucleic acid particles to undergo lipid mixing and fusion with adjacent membranes, and how phosphatidylethanolamine and other lipids may act as factors capable of disrupting bilayer structure and the endosomal pathway. Finally, we consider the challenges that remain in bringing nucleic acid based drugs into the realm of clinical reality.
Biophysical Journal | 1995
Barbara Mui; Hans-Günther Döbereiner; Thomas D. Madden; Pieter R. Cullis
The morphological consequences of differences in the monolayer surface areas of large unilamellar vesicles (LUVs) have been examined employing cryoelectron microscopy techniques. Surface area was varied by inducing net transbilayer transport of dioleoylphosphatidylglycerol (DOPG) in dioleoylphosphatidylcholine (DOPC):DOPG (9:1, mol:mol) LUVs in response to transmembrane pH gradients. It is shown that when DOPG is transported from the inner to the outer monolayer, initially invaginated LUVs are transformed to long narrow tubular structures, or spherical structures with one or more protrusions. Tubular structures are also seen in response to outward DOPG transport in DOPC:DOPG:Chol (6:1:3, mol:mol:mol) LUV systems, and when lyso-PC is allowed to partition into the exterior monolayer of DOPC:DOPG (9:1, mol:mol) LUVs in the absence of DOPG transport. Conversely, when the inner monolayer area is expanded by the transport of DOPG from the outer monolayer to the inner monolayer of non-invaginated LUVs, a reversion to invaginated structures is observed. The morphological changes are well described by an elastic bending theory of the bilayer. Identification of the difference in relaxed monolayer areas and of the volume-to-area ratio of the LUVs as the shape-determining factors allows a quantitative classification of the observed morphologies. The morphology seen in LUVs supports the possibility that factors leading to differences in monolayer surface areas could play important roles in intracellular membrane transport processes.
Archive | 1995
Steven M. Ansell; Barbara Mui; Michael J. Hope
Biophysical Journal | 1993
Barbara Mui; Pieter R. Cullis; Evan Evans; Thomas D. Madden
Methods in Enzymology | 2003
Barbara Mui; Laurie Chow; Michael J. Hope
Archive | 2009
Michael J. Hope; Sean C. Semple; Jianxin Chen; Thomas D. Madden; Pieter R. Cullis; Marco A. Ciufolini; Barbara Mui
Journal of Pharmacology and Experimental Therapeutics | 2001
Barbara Mui; Sameersingh G. Raney; Sean C. Semple; Michael J. Hope
Molecular Membrane Biology | 1999
Norbert Maurer; Atsu Mori; Lorne R. Palmer; Myrna A. Monck; Kenneth W. C. Mok; Barbara Mui; Quet F. Akhong; Pieter R. Cullis
Archive | 2008
Michael J. Hope; Sean C. Semple; Jianxin Chen; Thomas D. Madden; Barbara Mui; Pieter R. Cullis; Marco A. Ciufolini; Kim F. Wong; Muthiah Manoharan; Kallanthottathil G. Rajeev; Masunu Srinivasulu
Archive | 2000
Sean C. Semple; Troy Harasym; Sandra K. Klimuk; Ljiljiana D. Kojic; Jonathan L. Bramson; Barbara Mui; Michael J. Hope