Biomedical Engineering Reference
In-Depth Information
by upregulation of gene expression in a given cell type. Such
versatility
was
demonstrated
with
98N
-5,
which
delivered
12
42
34
siRNAs to address pathologies as diverse as cancer,
malaria,
and
27
hypercholesterolemia.
While potent and durable gene silencing
has been established upon delivery of siRNA to hepatocytes, realizing
the full potential of RNAi will require the synthesis of materials and
development of appropriate
screening assays to facilitate the
identification of new compounds that avoid uptake by hepatocytes
and confer silencing in other cell types at low doses. Serum-based
in vivo
Figure 7.5
Iterative library design. Starting components should be
selected rationally, based on previous studies or interesting
chemical structure. After ensuring the components can be
conjugated using efficient chemistry, efficient
screens
should be used to identify successful candidates. The top-
performing materials can be analyzed to determine structure-
function relationships. These results should inform the synthesis
of iterative libraries and the selection of compounds screened
in vitro
in
vivo
compound is identified, any excipients
used in its formulation should be systematically varied, and the
minimum carrier:siRNA mass ratio can be determined.
. Once a potent
in vivo
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