Nanostructured Gyroid Cubic Lipid Phases Containing Functional
RNA Molecules: Pore Forming Lipids Facilitate Release of RNA
Through Cellular Membranes Cyrus R. Safinya, University of
California-Santa Barbara, DMR 0803103 Figure 1. The gyroid lipid
cubic phase incorporating functional RNA within its two (green and
orange) water channels. A lipid bilayer surface separates the two
intertwined but independent water channels. For clarity, the
bilayer (which has an unusual saddle-splay shape) is represented by
a surface (gray) corresponding to a thin layer in the center of the
membrane as indicated in the enlarged inset. The novel structure,
termed Q II G, siRNA, was derived by use of synchrotoron x-ray
scattering methods at the Stanford Synchrotron Radiation
Laboratory. (Adapted from C. Leal et al., J. Am. Chem. Soc. 2010,
132, 16841, DOI: 10.1021/ja1059763, and Langmuir 2011, 27, 7691.
DOI: 10.1021/la200679x).10.1021/ja105976310.1021/la200679x The use
of cationic lipids as biomimetic synthetic carriers of nucleic
acids in cell-based delivery applications is currently
unprecedented. The range of applications dependent on efficient
nucleic acid delivery ranges from therapeutics (with DNA genes) to
functional genomics and biotechnology (with gene silencing RNA).
Nevertheless, our ability to design lipid-carriers of nucleic
acids, able to enter cells by punching holes in the membranes of
internal cellular components (which trap the carriers upon cell
entry), is the current limiting step in the development of gene
delivery/gene silencing technology. Employing a physicochemical
approach our study led to the discovery of a method to produce a
novel bicontinuous gyroid cubic lipid phase, which incorporates
functional RNA molecules for gene silencing (Figure 1). The complex
structure of the Gyroid Cubic phase was derived by our group using
state-of-the-art synchrotron x-ray scattering methods at the
National Facility at the Stanford Synchrotron Radiation Laboratory.
The paper demonstrates the remarkable properties of the lipid cubic
phase-RNA complex in efficient cell delivery and sequence- specific
gene silencing. This significant finding is consistent with the
hypothesis that cubic phase lipids have pore forming abilities
because of their unusual saddle-splay membrane shape (gray surface
in Figure 1). The work was reported in the Journal of the American
Chemical Society and Langmuir (C. Leal et al., JACS 2010, 132,
16841, and Langmuir 2011, 27, 76917697).
Slide 2
Education and Outreach Research Training: A Biomolecular
Materials Emphasis Cyrus R. Safinya, University of California-Santa
Barbara, DMR 0803103 Education: Undergraduate and graduate
students, and postdoctoral scholars with backgrounds in materials
science, physics, chemistry, and biology, are educated in methods
to discover natures rules for assembling molecular building blocks
in distinct shapes and sizes for particular functions. The learned
concepts enable development of advanced nanoscale materials for
broad potential applications in electronic, chemical, and
pharmaceutical industries. Outreach/Participation of undergraduate
and underrepresented students: Visiting graduate student Janos
Kayser participated in experimental studies of the structure and
phase behavior of Keratins (an important intermediate filament)
with Joanna Deek. Janos is currently obtaining his PhD degree from
the Technical University of Munich under the supervision of
Professor Andreas Bausch who spent a short sabbatical in our group.
(For more information see
http://www.mrl.ucsb.edu/safinyagroup/undergrads.htm) Julia
Korolenko (left, top photo), a recent undergraduate transfer
student from Santa Barbara City College (and a former INSET intern
(Internships in Nanosystems, Science, Engineering, and Technology)
with our group) is now engaged in research training while
simultaneously pursuing her undergraduate degree in Chemistry and
Biochemistry at UCSB. She is being trained, by Chemistry graduate
student Joanna Deek (2nd from left, top photo), in studies
invovling the structure and phase behavior of mixtures of
nuerofilaments and microtubules, which mimic the cytoskeletal
proteins of neurons. Thomas Oyuela-Trachter (right, top photo), a
senior undergraduate student at UCSB (Molecular, Cellular, &
Developmental Biology Depart.), participated in the CAMP
(California Alliance for Minority Participation) summer internship
program. He was mentored by physics graduate student Peter Chung
(second from right, top photo). His project focused on the
real-space imaging of microtubule-tau protein complexes, which
might elucidate interactions critical to understanding neuron
axonal growth and diseases like Alzheimer's related to tau-protein
malfunction. Jose Lopez (right, bottom photo, pictured with physics
graduate student Ramsey Majzoub), a UCSB undergraduate student
majoring in Mechanical Engineering, worked for three quarters in
the group (under the mentorship of Dr. Youli Li, Manager of the MRL
X-ray Facility) helping with design and construction of a new SAXS
instrument to characterize nanoscale assemblies. He is starting
graduate school this Fall at San Diego State University.