Hello bexster
Firstly, to answer your question about starburst dendrimers,
"Starburst Dendrimers are a class of polymeric macromolecules which
are defined by their regular, highly branched architectures. They are
characterized by their high molecular weight; the process of making
dendrimers yields the ability of ensuring very specific molecular
weights and uniform sizes. Dendrimers are envisioned to be tomorrow's
drug delivery agents, information processing materials, and
high-performance polymers." This quotation comes from the web site of
Chris Martin at Department of Chemistry, UC San-Diego,
http://grimace.ucsd.edu/dendrimer/dendrimer.html. It contains links
to research centres and researchers interested in dendrimers.
However, the page was last updated in 1998, so some of this
information might no longer be valid.
An account of how a scientist at York University developed a simpler
method of producing starburst dendrimers, starting with lysine as a
building block, can be found in the November 1999 issue of Elemental
Discoveries at http://www.sciencebase.com/nov99_iss2.html (Scroll
about two-thirds down the page until you get to the title To Dye For).
The article mentions that these materials were first prepared by IBM
scientist Donald Tomalia in the 1980s.
A more-detailed description of starburst dendrimers, with diagrams, is
available in a pdf document from the Helmholtz Research Centre in
Julich, Germany (http://www.fz-juelich.de/iff/Institute/iwm/Research/r1/dynamics_and_structure.pdf.)
I am having problems downloading pdf at the moment and wasn't able to
open this document. Instead I looked at Google's HTML cache, which
unfortunately does not display the illustrations. However, if you too
have difficulties with the pdf file, the cache is at
http://216.239.39.100/search?q=cache:HXTSVum2gBYC:www.fz-juelich.de/iff/Institute/iwm/Research/r1/dynamics_and_structure.pdf+starburst+dendrimers&hl=en&ie=UTF-8
The papers I mentioned in my clarification request are:
Delivery of Genes via Liposomes to Corneal Endothelial Cells
by Uwe Pleyer and Haike Dannowski
Drug News & Perspectives Vol. 15, No. 5, June 2002
The authors say: “Compared with viral vectors, liposomes are
particularly suitable with respect to simplicity of preparation,
large-scale production and their lack of specific immune response.
After systemic administration, however, a lower transfection
efficiency as compared with viral systems and a transient gene
expression limit their use. We therefore focus on organ specific, ex
vivo gene therapy to prevent tissue or organ damage of the eye.”
Summary at: http://www.prous.com/journals/dnp/20021505/summary/dn0283.cfm
Subscription required for the full text, which is available as HTML or
pdf.
Journal of Drug Targeting 2000;7(6):413-21
Gene delivery and expression in human retinal pigment epithelial
cells: effects of synthetic carriers, serum, extracellular matrix and
viral promoters.
Urtti A, Polansky J, Lui GM, Szoka FC.
Department of Bio-Pharmaceutical Sciences, University of California
San Francisco, USA.
“Non-viral gene therapy is a potential treatment to many incurable
retinal diseases. To fulfill this promise, plasmid DNA must be
delivered to the retinal target cells. We evaluated the efficacy of
synthetic DNA complexing compounds in transfecting primary human
retinal pigment epithelial (RPE) cells in vitro… … Plasmids encoding
nuclear localizing beta galactosidase or luciferase (pRSVLuc, pCLuc4,
pSV2Luc) were complexed in water at various +/- charge ratios using
cationic lipids (Lipofectin, DOTAP, DOGS), polyethylene imines (25 and
750 kDa), and with degraded 6th generation starburst polyamidoamine
dendrimers…. … Degraded dendrimers and high molecular weight PEI
exhibited the best combination of high activity and low toxicity in
RPE cell transfection.”
Current Eye Research 2000 May;20(5):361-6
Optimization of non-viral gene transfer to human primary retinal
pigment epithelial cells.
Abul-Hassan K, Walmsley R, Boulton M.
University Department of Ophthalmology, Manchester Royal Eye Hospital,
Manchester, United Kingdom.
“PURPOSE: To optimise the high efficiency, non-viral transfer of DNA
to retinal pigment epithelial (RPE) cells in vitro… … Liposomes-based
methods successfully transferred the vector to RPE cells, but the
efficiency varied for different liposomes; Tfx-50 > Lipofectin >
Lipofectamine > Cellfectin > DMRIE-C. No significant cytotoxicity was
observed with any of the liposome treatments. Optimal transfection was
achieved with Tfx-50 at a 3:1 ratio of DNA:liposome; between 12-15% of
cells being transfected. CONCLUSIONS: Efficient and non-toxic transfer
of functional genes into primary RPE cells in vitro can be successfuly
achieved by liposomes-based techniques. Tfx-50 appears to be a
promising non-viral vector for RPE gene transfer.”
The second and third paper were found on a PubMed Medline search
(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed). Here are
the links to the abstracts:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10758912&dopt=Abstract
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10855030&dopt=Abstract
And here is a further paper:
Exp Eye Res 2001 Jul;73(1):1-7
Efficiency and toxicity of liposome-mediated gene transfer to corneal
endothelial cells.
Pleyer U, Groth D, Hinz B, Keil O, Bertelmann E, Rieck P, Reszka R.
Department of Ophthalmology, Charite, Campus Virchow, Humboldt
University, Augustenburger Platz 1, D-13353 Berlin, Germany.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11428857&dopt=Abstract
For general information about gene therapy, the Journal of Young
Investigators has a useful article at
http://www.jyi.org/issues/currentIssue/features/lovejoy.html (Gene
Therapy: Techniques of Cell Transfection by Katherine Lovejoy,
Northwestern University)
and another on the web site of Industry Canada
http://strategis.ic.gc.ca/SSG/tc00011e.html (What is Gene Therapy)
A press release from Stanford: STANFORD RESEARCHERS DEVISE NOVEL GENE
THERAPY TECHNIQUE (dated 9/15/02)
http://mednews.stanford.edu/news_releases_html/2002/sepreleases/RDEB_genetherapy.html
and a ScienceDaily report "In Gene Therapy First, Scientists Restore
Vision To Dogs Born Blind"
http://www.sciencedaily.com/releases/2001/04/010430072552.htm (also
contains a link to the original press release describing this
breakthrough)
Search strategies:
On PubMed Medline: gene + eye + liposomes
On Google: 1. "starburst dendrimers"
2. "gene therapy" eye
3. "gene therapy" techniques
I hope this gives you some of the information that you are seeking.
Please request further clarification if you are not satisfied with
this answer. |
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