VNPs as Tools for Nanomedicine - Viral Nanoparticles: Tools for Materials Science and Biomedicine - page 229

Besides covalently attaching drugs to the VNP surface, the drug can also
be encapsulated into the VNP interior's cavity, thus protecting the molecules.
The drug doxorucicin has been encapsulated in RCNMV and HCRSV (recall
Chapter 5) (Loo ., 2007). Combining targeting and

therapy, doxorubicin-encapsulating FA-targeted VNPs have been made using
HCRSV.

et al ., 2008; Ren et al

In vitro studies confirmed specific cellular uptake and cytoxicity

(Ren ., 2007).

Similarly, dual functionalized MS2 particles were constructed and
tested. Here, the drug was encapsulated by covalently linking it to the RNA
stem loop operator (recall Section 5.1.1). Encapsulation of the toxin ricin
A and the nucleotide analog 5-fluoruoridine was achieved; 90 molecules
per particle can be packed (the RNA stem loops bind to every coat protein
dimer; MS2 consist of 90 dimers) (Brown

et al

., 2002). Specific targeting was
facilitated using either specific antibodies or Tf. Cell delivery and cytotoxity
were shown

et al

., 2002).
In summary, many different strategies have been developed that allow
the fabrication of dual-functionalized VNPs with potential for site-specific
drug delivery. Future studies will undoubtedly provide insights into the
performance and efficacy of such materials

in vitro (Brown et al

in vivo .

. gene delIVery And gene SIlenCIng

Genetic disorders may involve the over- or underexpression of endogenous
genes, and therapy then becomes a matter of silencing or complementing
endogenous gene expression. Silencing strategies involve either direct
steric inhibition of the translational machinery by the introduction of
anti-sense RNA strands complementary to the (mRNA), or

targeting the mRNA transcript for degradation via the Dicer pathway using
small interfering

messenger RNA

RNAs (siRNAs). Upregulation by contrast involves directly
introducing genes into the patient for subsequent expression.
Cellular targeting of either strategy has been employed in viral and non-
viral systems. Non-viral methodologies include liposomal or polymeric
coated nucleic acids, whereas much of the literature among viral targeting
methods has focused on the potential of Ads, AAV, and . The use

of virus-mediated gene delivery is an extensive field; a recent PubMed
search yielded thousands of articles. The reader is referred to the following
excellent reviews (Ali

Lentivirus

2

et al ., 1994; Barzon et al ., 2005; Benihoud et al .,

1999; Choi et al ., 2005; Cockrell & Kafri, 2007; Douglas, 2004; Kafri, 2004;

Kapturczak et al ., 2001; Liu & Kirn, 2008; Sharma et al ., 2009; Tenenbaum et

al ., 2004).