Biomedical Engineering Reference
In-Depth Information
7.8.2.9 Light-Mediated Antisense Drug Delivery
Caged oligonucleotides are one of the most recently reported chemically modified AS
ODNs for targeted oligonucleotide delivery. Monroe et al. and Coll et al. described the
photocaging spatiotemporal strategy, which makes use of a photolytic chromophore
for rapid release of a biologically active substrate on exposure to light [190,191] . This
caging involves covalent attachment of photolabile compounds to effector nucleic acid
species that block the bioactivity until triggered by near-ultraviolet light. Photocaging
also protects the effector nucleic acid from nuclease and blocks its native bioactivity
until exposed to near-ultraviolet light. This phenomenon was first used by Kaplan et
al. to release an inducer in the biological environment [192] . The various types of cage
compounds commonly used with an effector nucleic acid are summarized in Fig. 7.7 .
Recently, Deiters's Group has made NPOM (nitropiperonyloxymethyl)-caged dT
phosphoramidite for light-mediated delivery of phosphoramidite oligonucleotides
commercially available [193] .
7.8.2.10 Other Delivery Techniques
In addition to the delivery technologies discussed earlier, some other practices have
also been reported, including the use of nonprotein alternatives to antibiotics, that is,
CH 3
X
H 3 CO
X
X
No 2
H 3 CO
No 2
No 2
(A)
(B)
(C)
CH 3
CH 3
CH 3
H 3 CO
O
X
X
X
O
H 3 CO
No 2
No 2
No 2
(D)
(E)
(F)
R 2
X
O
HO
O
R 2
O
O
R 1
R 1
R 1
R 2
X
X
(G)
(H)
(I)
Figure 7.7 Common cage compounds (A) NB (nitrobenzyl), (B) DMNB (dimethoxy-
nitrobenzyl), (C) NPP (nitrophenylpropyl), (D) NPE (nitrophenylethyl), (E) DMNPE
(dimethoxy-nitrophenylethyl), (F) NPOM (6-nitropiperonyloxymethyl), (G) pHP
( p -hydroxyphenacyl), (H) benzoin, and (I) coumarinyl.
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