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M. Irfan et al.
different binding domains on the 5B polymerase, and a non-competitive binding
of aptamer B.2. to the RNA polymerase was observed, which weakens the enzyme
activity [82–84]. Two RNA aptamers specific to the non-structural 5B polymerase
27v and 127v caused the in vitro inhibition of HCV polymerase activity. The aptamer
27v was reported to block the initiation and the elongation of viral RNA transcription
as competitive binder for the binding sites of the polymerase, while the aptamer 127v
was observed to inhibit the initiation and post-initiation events [85].
An aptamer No. 28 limited the assembly of hepatitis B virus (HBV) nucleocapsid
in an efficient way and suppressed the viral replication [86] because the HBV core
protein has an important role in the production of the HBV nucleocapsid and viral
assembly [87]. Similarly, a peptide aptamer was designed against HBV core protein
which reduced the viral replication under intracellular conditions by affecting capsid
formation [88]. RNA aptamers specific to the HIV nucleocapsid protein were selected
for arresting the viral assembly. These aptamers were supposed to compete with the
psi RNA [89]. The retroviral psi elements are cis-acting RNA inside the genome of
HIV with a functional role in regulating the assembly of the viral genome during
replication. In addition, the HIV-1 nucleocapsid protein is a crucial member in the
encapsulation of viral genome [90]. In previous outbreak of SARS 2007 an RNA
aptamer against SCV NTPase/Helicase (nsP10) was selected and it was observed that
it efficiently inhibited the double-stranded DNA unwinding activity of the helicase
by approximately 85% with an IC 50 value of 1.2 nM [91].
7.2.2.3 Aptamers Against Other Diseases
Aptamers Against Age-Related Macular Degeneration
The first commercialized RNA-aptamer-based drug was Macugen (pegaptanib)
which is used for the treatment of age-related macular degeneration (AMD). Vascular
endothelial growth factor (VEGF) is responsible for pathological ocular neovascularization and vascular permeability, and pegaptanib selectively binds to VEGF-165.
When pegaptanib was cocultured with human umbilical vein endothelial cells, it
inhibited an interaction of
125 I-labeled VEGF with half maximal inhibitory concentration (IC 50 ) of 0.75–1.4 nM. The reported elimination half-lives of pegaptanib in
rhesus monkeys were 9.3 h after intravenous and 12 h after a subcutaneous administration (1 mg/kg). Population pharmacokinetic studies in patients with neovascular AMD or diabetic macular edema indicated pegaptanib did not accumulate in
the plasma after multiple doses. It was also recorded that there was no significant
impact of race, gender, glaucoma, and hypertension on the pharmacokinetic (PK) of
pegaptanib [92].
M. Irfan et al.
different binding domains on the 5B polymerase, and a non-competitive binding
of aptamer B.2. to the RNA polymerase was observed, which weakens the enzyme
activity [82–84]. Two RNA aptamers specific to the non-structural 5B polymerase
27v and 127v caused the in vitro inhibition of HCV polymerase activity. The aptamer
27v was reported to block the initiation and the elongation of viral RNA transcription
as competitive binder for the binding sites of the polymerase, while the aptamer 127v
was observed to inhibit the initiation and post-initiation events [85].
An aptamer No. 28 limited the assembly of hepatitis B virus (HBV) nucleocapsid
in an efficient way and suppressed the viral replication [86] because the HBV core
protein has an important role in the production of the HBV nucleocapsid and viral
assembly [87]. Similarly, a peptide aptamer was designed against HBV core protein
which reduced the viral replication under intracellular conditions by affecting capsid
formation [88]. RNA aptamers specific to the HIV nucleocapsid protein were selected
for arresting the viral assembly. These aptamers were supposed to compete with the
psi RNA [89]. The retroviral psi elements are cis-acting RNA inside the genome of
HIV with a functional role in regulating the assembly of the viral genome during
replication. In addition, the HIV-1 nucleocapsid protein is a crucial member in the
encapsulation of viral genome [90]. In previous outbreak of SARS 2007 an RNA
aptamer against SCV NTPase/Helicase (nsP10) was selected and it was observed that
it efficiently inhibited the double-stranded DNA unwinding activity of the helicase
by approximately 85% with an IC 50 value of 1.2 nM [91].
7.2.2.3 Aptamers Against Other Diseases
Aptamers Against Age-Related Macular Degeneration
The first commercialized RNA-aptamer-based drug was Macugen (pegaptanib)
which is used for the treatment of age-related macular degeneration (AMD). Vascular
endothelial growth factor (VEGF) is responsible for pathological ocular neovascularization and vascular permeability, and pegaptanib selectively binds to VEGF-165.
When pegaptanib was cocultured with human umbilical vein endothelial cells, it
inhibited an interaction of
125 I-labeled VEGF with half maximal inhibitory concentration (IC 50 ) of 0.75–1.4 nM. The reported elimination half-lives of pegaptanib in
rhesus monkeys were 9.3 h after intravenous and 12 h after a subcutaneous administration (1 mg/kg). Population pharmacokinetic studies in patients with neovascular AMD or diabetic macular edema indicated pegaptanib did not accumulate in
the plasma after multiple doses. It was also recorded that there was no significant
impact of race, gender, glaucoma, and hypertension on the pharmacokinetic (PK) of
pegaptanib [92].