422
H. Jin
[92] in patient with a TTP, seven patients with a TTP received combined therapy with
intravenous ARC1779 injections and plasma exchange, the result shows no severe
adverse events.
Sakai et al. [93] developed a novel DNA aptamer, TAGX-0004, to the VWF A1
domain; it contains an artificial base and demonstrates high affinity to VWF.TAGX0004 showed stronger inhibition of thrombus formation than ARC1779 and had
comparable inhibitory effects to caplacizumab suggested that TAGX-0004 might be
similarly promising for a TTP treatment.
14.3.2.4 Infection-Related Disease
Aptamer has been successfully used in the diagnostic of infection-related disease.
Such as detection of L. monocytogenes [94], profoundly invasive candidiasis,etc.
[95]. but, aptamer used as target therapy in infection-related disease is limited.
Teamwork from University of Leeds [96, 97] described an HPV16 E7 aptamer
(termed A2) as molecular tools to target the cellular function of the HPV E7 oncoprotein. The result showed that transfection of CaSki cells with the aptamer A2 could
induce apoptosis in HPV-transformed cells to accompany with decrease of E7 level
and increase pRb.
Another high affinity RNA aptamer (Sc5c3) is specific for HPV16 L1 virus-like
particles (VLPs). Valencia-Reséndiz et al. [98] report the inhibition of HPV16 infection by Sc5c3 in a pseudovirus (PsVs) model. Incubation of HPV16 PsVs with Sc5c3
before infection resulted in a dose-dependent decrease in report gene, suggesting
infection inhibition. Aptamer degradation by RNase A restored PsVs infectivity,
supporting the previous observation that Sc5c3 aptamer can inhibit infection of HPV.
14.3.2.5 Cancer
Owing to its unique characteristics (high affinity binding, low immunogenicity, ease
of synthesis, and chemical modification), aptamers have evolved rapidly and highlighted as the next generation of anticancer drugs. Aptamers target a broad range
of molecules involving in tumor progression and metastasis. Preclinical and clinical
investigations of aptamers have shown their efficacies as well as safety profiles.
Although only limited aptamers have already launched clinical trials, mounting
evidence support that aptamers have an exceptional opportunity to make personalized
medicine a reality for more patients with cancer.
AS1411 is a first-in-class quadruplex DNA aptamer formed from a singlestranded, G-rich, phosphodiester, 26-mer oligonucleotide [99]. It targets nucleolin,
a multifunctional protein located primarily in the nucleolus, and is overexpressed in
many types of cancers [100, 101]. AS1411 can induce apoptosis directly by binding to
tumor cell-surface nucleolin [102] and can work as delivery vehicles for therapeutic
agents by internalizing into the nucleolin expressing cells. AS1411 is the first aptamer
in clinical trials for cancer treatment. Patients with metastatic or inoperable locally
H. Jin
[92] in patient with a TTP, seven patients with a TTP received combined therapy with
intravenous ARC1779 injections and plasma exchange, the result shows no severe
adverse events.
Sakai et al. [93] developed a novel DNA aptamer, TAGX-0004, to the VWF A1
domain; it contains an artificial base and demonstrates high affinity to VWF.TAGX0004 showed stronger inhibition of thrombus formation than ARC1779 and had
comparable inhibitory effects to caplacizumab suggested that TAGX-0004 might be
similarly promising for a TTP treatment.
14.3.2.4 Infection-Related Disease
Aptamer has been successfully used in the diagnostic of infection-related disease.
Such as detection of L. monocytogenes [94], profoundly invasive candidiasis,etc.
[95]. but, aptamer used as target therapy in infection-related disease is limited.
Teamwork from University of Leeds [96, 97] described an HPV16 E7 aptamer
(termed A2) as molecular tools to target the cellular function of the HPV E7 oncoprotein. The result showed that transfection of CaSki cells with the aptamer A2 could
induce apoptosis in HPV-transformed cells to accompany with decrease of E7 level
and increase pRb.
Another high affinity RNA aptamer (Sc5c3) is specific for HPV16 L1 virus-like
particles (VLPs). Valencia-Reséndiz et al. [98] report the inhibition of HPV16 infection by Sc5c3 in a pseudovirus (PsVs) model. Incubation of HPV16 PsVs with Sc5c3
before infection resulted in a dose-dependent decrease in report gene, suggesting
infection inhibition. Aptamer degradation by RNase A restored PsVs infectivity,
supporting the previous observation that Sc5c3 aptamer can inhibit infection of HPV.
14.3.2.5 Cancer
Owing to its unique characteristics (high affinity binding, low immunogenicity, ease
of synthesis, and chemical modification), aptamers have evolved rapidly and highlighted as the next generation of anticancer drugs. Aptamers target a broad range
of molecules involving in tumor progression and metastasis. Preclinical and clinical
investigations of aptamers have shown their efficacies as well as safety profiles.
Although only limited aptamers have already launched clinical trials, mounting
evidence support that aptamers have an exceptional opportunity to make personalized
medicine a reality for more patients with cancer.
AS1411 is a first-in-class quadruplex DNA aptamer formed from a singlestranded, G-rich, phosphodiester, 26-mer oligonucleotide [99]. It targets nucleolin,
a multifunctional protein located primarily in the nucleolus, and is overexpressed in
many types of cancers [100, 101]. AS1411 can induce apoptosis directly by binding to
tumor cell-surface nucleolin [102] and can work as delivery vehicles for therapeutic
agents by internalizing into the nucleolin expressing cells. AS1411 is the first aptamer
in clinical trials for cancer treatment. Patients with metastatic or inoperable locally