340
Y. Cheng and H. Jin
11.3.3.3 Application of Aptamer in Diabetes Mellitus
With the improvement of people’s living quality, the number of diabetes mellitus
patients is increasing rapidly. Diabetes mellitus is a disease characterized by polydipsia, polyphagia, polyuria, emaciation, and weakness. Type 2 diabetes mellitus
(T2DM) has multiple causes, including genetic and environmental factors. People
who are affected by T2DM may suffer from β-cell dysfunction, insulin resistance,
and chronic inflammation. It is estimated that the number of people with T2DM may
rise to 592 million by 2035 [96]. T2DM begins with insulin resistance, a condition
in which cells fail to respond to insulin properly. As the disease progresses, a lack
of insulin may also develop.
Spiegelmers are synthetic oligonucleotides built from L-nucleotides [97]. The
mirror-image aptamers are more stable and not easily degraded by internal and
external nucleases [97, 98], and are more suited for in vitro and in vivo applications. NOX-E36 is a left-handed RNA aptametar getting human chemokine CCL2
and related chemokines [98, 99] (Fig. 11.6). It can antagonize the CCL2/CCR2 axis
in humans. It has anti-inflammatory properties that prevent pro-inflammatory cells
from infiltrating into the kidney and resolve existing inflammation. NOX-E36 has
completed a Phase IIa study for the treatment of diabetic nephropathy [100].
11.4 Overcome the Restrictions for Commercial Use
of Aptamers
Aptamer has become a promising research field since its emergence in 1990. The high
affinity and specificity of aptamers make them ideal diagnostic reagents. Depending
on their ligand-induced conformational changes that can be identified by differential dye binding, fluorescence quenching, or fluorescence resonance energy transfer,
aptamers can be applied to multiple fields, ranging from detection, diagnosis, to
treatments in medical science.
However, compared to other methods, aptamers do have many undeniable disadvantages. Because of the susceptibility of aptamers to degradation by nucleases,
their rapid renal filtration, suboptimal thermal stability, and the lack of functional
group diversity, aptamers have not been put into the commercial market massively,
summarized as follows are some research attempts or schemes to address the
abovementioned issues, accordingly.
Firstly, in order to prolong the half-life period of aptamers in the human body,
nucleotides should be bridged, locked, or modified at sugar moieties or internucleotide–phosphodiester linkages. Unmodified nucleic acids generally decay after
5 min in serum [101] and less than an hour in living cells [102]. Chemically modifying aptamers is the most common strategy to solve this problem. The most widely
used modifications are nucleotides with fluoro or O-methyl groups at the 2
-O position of their sugar moiety. For example, 2
-Amino pyrimidine nucleosides [103],
Y. Cheng and H. Jin
11.3.3.3 Application of Aptamer in Diabetes Mellitus
With the improvement of people’s living quality, the number of diabetes mellitus
patients is increasing rapidly. Diabetes mellitus is a disease characterized by polydipsia, polyphagia, polyuria, emaciation, and weakness. Type 2 diabetes mellitus
(T2DM) has multiple causes, including genetic and environmental factors. People
who are affected by T2DM may suffer from β-cell dysfunction, insulin resistance,
and chronic inflammation. It is estimated that the number of people with T2DM may
rise to 592 million by 2035 [96]. T2DM begins with insulin resistance, a condition
in which cells fail to respond to insulin properly. As the disease progresses, a lack
of insulin may also develop.
Spiegelmers are synthetic oligonucleotides built from L-nucleotides [97]. The
mirror-image aptamers are more stable and not easily degraded by internal and
external nucleases [97, 98], and are more suited for in vitro and in vivo applications. NOX-E36 is a left-handed RNA aptametar getting human chemokine CCL2
and related chemokines [98, 99] (Fig. 11.6). It can antagonize the CCL2/CCR2 axis
in humans. It has anti-inflammatory properties that prevent pro-inflammatory cells
from infiltrating into the kidney and resolve existing inflammation. NOX-E36 has
completed a Phase IIa study for the treatment of diabetic nephropathy [100].
11.4 Overcome the Restrictions for Commercial Use
of Aptamers
Aptamer has become a promising research field since its emergence in 1990. The high
affinity and specificity of aptamers make them ideal diagnostic reagents. Depending
on their ligand-induced conformational changes that can be identified by differential dye binding, fluorescence quenching, or fluorescence resonance energy transfer,
aptamers can be applied to multiple fields, ranging from detection, diagnosis, to
treatments in medical science.
However, compared to other methods, aptamers do have many undeniable disadvantages. Because of the susceptibility of aptamers to degradation by nucleases,
their rapid renal filtration, suboptimal thermal stability, and the lack of functional
group diversity, aptamers have not been put into the commercial market massively,
summarized as follows are some research attempts or schemes to address the
abovementioned issues, accordingly.
Firstly, in order to prolong the half-life period of aptamers in the human body,
nucleotides should be bridged, locked, or modified at sugar moieties or internucleotide–phosphodiester linkages. Unmodified nucleic acids generally decay after
5 min in serum [101] and less than an hour in living cells [102]. Chemically modifying aptamers is the most common strategy to solve this problem. The most widely
used modifications are nucleotides with fluoro or O-methyl groups at the 2
-O position of their sugar moiety. For example, 2
-Amino pyrimidine nucleosides [103],