80
Z. Liu and Y. Liu
to bind with the c-Met protein, thus inhibiting cell prolification, differentiation and
migration. The DNA aptamer shows great potential as novel therapeutic option for
cancer therapy (Fig. 4.1b) [24]. FOXM1 is a member of the forkhead/winged-helix
transcription factor family associated with DNA replication and mitosis. Xiang et al.
reported that FOXM1 specific aptamer can colocalize with FOXM1 in the nucleus
and showed inhibition on transcription and expression of FOXM1 genes, leading
to the suppression of cell proliferation. Another aptamer screened for forkhead box
1 (FOXM1) was also reported to have cell proliferation inhibitory function [25].
Besides, an anti-PCNA aptamer was reported to compete with the primer-template
DNA for binding to the PCNA/DNA polymerase complex, which caused inhibition
of DNA replication (Fig. 4.1c) [26]. Very recently, Giangrande et al. [27] selected an
aptamer which binded to those histones responsible for multiple argan dysfunction
syndrome (MODS) without nonspecific serum proteins’ binding. The neutralization of histones by chemically stabilized aptamers decreased patient morbidity and
mortality in a murine model of MODS. These aptamers had great potential to achieve
significant therapeutic benefit in treating multiple diverse clinical conditions associated with MODS. A RNA aptamer (A9g) was screened to function as a smart
drug for treatment of prostate cancer by inhibiting the enzymatic activity of prostatespecific membrane antigen (PSMA) to reduce the cancer cell migration/invasion and
metastasis [28].
Programmed death-ligand 1 (PD-L1) was reported to be overexpressed in many
cancer cells, which help cancer cells to escape from immune system’s attack through
binding with PD-1, an immune-suppressive molecule of T cell receptor [29]. Therefore, developing effective PD-L1 antagonist is of great significance for immune
therapy of cancers. According to the recent work by Yang’s group, a PD-L1 specific
aptamer, called aptPD-L1, was found to block the binding between PD-1 and PDL1, and assist the T-cell function restoration, therefore promoting the lymphocyte
proliferation and inhibition of tumor growth (Fig. 4.1d) [30]. Yang et al. [31] developed a novel TNF-alpha-targeting aptamer (aptTNF-alpha) with antagonistic functions. They investigated the in vivo antagonistic effect using mouse acute lung injury
(ALI) and acute liver failure models (ALF). The results showed that aptTNF-alpha
possessed good binding affinity towards mouse TNF-alpha in vivo. The aptTNFalpha treatment attenuated the severity of ALI, including the reduction of protein-rich
fluid leakage and neutrophil infiltration in the spaces as well as the suppression of proinflammatory cytokines/chemokines expressions. The data implicated translational
potential roles of aptTNF-alpha as a TNF-alpa blocking agent.
Despite the rapid development of aptamer therapeutic agents has been witnessed
since 2004, finding aptamers with therapeutic effects other than binding ability is
often difficult. Additionally, specific pathological targets and subsequently cellular
signal pathways should be fully clarified. More importantly, the pharmacokinetics of
aptamer drugs, such as metabolic instability, renal filtration, nuclease degradation,
is also a big concern for clinical transformation.
Z. Liu and Y. Liu
to bind with the c-Met protein, thus inhibiting cell prolification, differentiation and
migration. The DNA aptamer shows great potential as novel therapeutic option for
cancer therapy (Fig. 4.1b) [24]. FOXM1 is a member of the forkhead/winged-helix
transcription factor family associated with DNA replication and mitosis. Xiang et al.
reported that FOXM1 specific aptamer can colocalize with FOXM1 in the nucleus
and showed inhibition on transcription and expression of FOXM1 genes, leading
to the suppression of cell proliferation. Another aptamer screened for forkhead box
1 (FOXM1) was also reported to have cell proliferation inhibitory function [25].
Besides, an anti-PCNA aptamer was reported to compete with the primer-template
DNA for binding to the PCNA/DNA polymerase complex, which caused inhibition
of DNA replication (Fig. 4.1c) [26]. Very recently, Giangrande et al. [27] selected an
aptamer which binded to those histones responsible for multiple argan dysfunction
syndrome (MODS) without nonspecific serum proteins’ binding. The neutralization of histones by chemically stabilized aptamers decreased patient morbidity and
mortality in a murine model of MODS. These aptamers had great potential to achieve
significant therapeutic benefit in treating multiple diverse clinical conditions associated with MODS. A RNA aptamer (A9g) was screened to function as a smart
drug for treatment of prostate cancer by inhibiting the enzymatic activity of prostatespecific membrane antigen (PSMA) to reduce the cancer cell migration/invasion and
metastasis [28].
Programmed death-ligand 1 (PD-L1) was reported to be overexpressed in many
cancer cells, which help cancer cells to escape from immune system’s attack through
binding with PD-1, an immune-suppressive molecule of T cell receptor [29]. Therefore, developing effective PD-L1 antagonist is of great significance for immune
therapy of cancers. According to the recent work by Yang’s group, a PD-L1 specific
aptamer, called aptPD-L1, was found to block the binding between PD-1 and PDL1, and assist the T-cell function restoration, therefore promoting the lymphocyte
proliferation and inhibition of tumor growth (Fig. 4.1d) [30]. Yang et al. [31] developed a novel TNF-alpha-targeting aptamer (aptTNF-alpha) with antagonistic functions. They investigated the in vivo antagonistic effect using mouse acute lung injury
(ALI) and acute liver failure models (ALF). The results showed that aptTNF-alpha
possessed good binding affinity towards mouse TNF-alpha in vivo. The aptTNFalpha treatment attenuated the severity of ALI, including the reduction of protein-rich
fluid leakage and neutrophil infiltration in the spaces as well as the suppression of proinflammatory cytokines/chemokines expressions. The data implicated translational
potential roles of aptTNF-alpha as a TNF-alpa blocking agent.
Despite the rapid development of aptamer therapeutic agents has been witnessed
since 2004, finding aptamers with therapeutic effects other than binding ability is
often difficult. Additionally, specific pathological targets and subsequently cellular
signal pathways should be fully clarified. More importantly, the pharmacokinetics of
aptamer drugs, such as metabolic instability, renal filtration, nuclease degradation,
is also a big concern for clinical transformation.