Biomedical Engineering Reference
In-Depth Information
nucleic acid is still a rate-limiting step for gene therapy. Here, we
have developed two types of membrane/core Nanoparticles (NPs) in
order to efficiently deliver siRNA and further its use in therapeutic
applications. The first LPD (Liposome-Polycation-DNA) formulation
showed efficient delivery of siRNA and a potential therapeutic
effect for metastatic lung tumor treatment. The second formulation,
referred to as LCP (Lipid-Calcium-Phosphate), was developed in
order to improve the limited release of cargo of LPD formulation,
which was done by replacing the protamine-DNA core with a pH-
sensitive calcium phosphate (CaP) core.
3.1
Introduction
Gene therapy has emerged as a promising means to treat various
genetic or acquired diseases by altering the genetic make-up of
cells. There are three essential types of nucleic acid drugs based
on their therapeutic relevance: gene inhibitors, gene vaccines, and
gene substitutes.
1
Among these, gene inhibitors, in particular, such
as single-stranded antisense oligonucleotide (ODN) and siRNA have
been intensively studied and are playing a major role in therapeutic
application for many disease treatments.
There are several ways to induce transient disruption of gene
expression and further generate a gene silencing effect, which has
extensive applications in biomedical research. The first method is
to inhibit the translation of a target gene by hybridizing it to the
corresponding mRNA using synthetic, small, and single-stranded
ODN.
2
Ribozyme, a RNA enzyme, can also be used to cleave single-
stranded regions in RNA through esterification or hydrolysis
reactions.
3, 4
Double-stranded siRNA shows an improved silencing
5
effect5
over ODN, with outstanding target specificity and stability in
serum. Aside from the improved efficiency on gene silencing, siRNA
has other advantages. It does not require a cellular expression
system, complex protein purification, or refolding schemes and
therefore leads to relatively uncomplicated synthesis. Thus,
siRNA has been widely considered as a promising candidate in
developing new therapeutic applications for various diseases. Short
hairpin RNA (shRNA) is converted to a siRNA duplex by a cellular
enzyme, Dicer, and is subsequently incorporated into target mRNA
degradation, leading to the silencing of a target gene. Unlike other
abundant cellular RNAs, shRNA is transcribed by RNA polymerase
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