• Source: L-Ribonucleic acid aptamer

An L-ribonucleic acid aptamer (L-RNA aptamer, trade name Spiegelmer) is an RNA-like molecule built from L-ribose units. It is an artificial oligonucleotide named for being a mirror image of natural oligonucleotides. L-RNA aptamers are a form of aptamers. Due to their L-nucleotides, they are highly resistant to degradation by nucleases. L-RNA aptamers are considered potential drugs and are currently being tested in clinical trials.




Features






= Chemical properties

=

L-RNA aptamers, built using L-ribose, are the enantiomers of natural oligonucleotides, which are made with D-ribose. Nucleic acid aptamers, including L-RNA aptamers, contain adenosine monophosphate, guanosine monophosphate, cytidine monophosphate, uridine monophosphate, a phosphate group, a nucleobase and a ribose sugar.




= Biological characteristics

=
Like other aptamers, L-RNA aptamers are able to bind molecules such as peptides, proteins, and substances of low molecular weight. The affinity of L-RNA aptamers to their target molecules often lies in the pico to nanomolar range and is thus comparable to antibodies.
L-RNA aptamers themselves have low antigenicity. In contrast to other aptamers, L-RNA aptamers have high stability in blood serum, since they are less susceptible to be cleaved hydrolytically by enzymes. They are excreted by the kidneys in a short time due to their low molar mass (which is below the renal threshold).
L-RNA aptamers modified with a higher molar mass, such as PEGylated L-RNA aptamers, show a prolonged plasma half-life.




Production


Unlike other aptamers, L-RNA aptamers are not directly made using systematic evolution of ligands by exponential enrichment (SELEX), as L-nucleic acids are not amenable to enzymatic methods, such as polymerase chain reaction (PCR), used in SELEX. Therefore, the selection is done with mirrored target molecules.




= Reflection of the target molecule

=
The first step is the production of the target's enantiomer. In the case of peptides and small proteins that are produced synthetically, an enantiomer is made using synthetic D-amino acids. If the target is a larger protein molecule, beyond synthetic abilities, the enantiomer of an epitope is produced.




= SELEX

=
Conventional (up to 1016 different oligonucleotides) existing molecule library serves as a starting point for the subsequent SELEX process. Selection, separation, and amplification using the mirror image of the target molecule is performed.




= Sequencing and synthesis

=
The sequence of the oligonucleotide selected using SELEX is determined with the help of DNA sequencing. This information is used for the synthesis of the oligonucleotide's enantiomer, the L-RNA aptamer, using L-nucleotides.




Use


L-RNA aptamers have been obtained for the chemokines CCL2 and CXCL12, the complement components C5a and ghrelin. They are currently in preclinical or clinical development. Proof-of-concept for an anti-CCL2/MCP-1 L-RNA aptamers has recently been demonstrated in diabetic nephropathy patients. They can also be used as diagnostic agents.




References

Kata Kunci Pencarian:

• L-Ribonucleic acid aptamer
• RNA
• DNA
• RNA therapeutics
• Mirror life
• Nucleic acid tertiary structure
• Hachimoji DNA
• Genetic code
• PreQ1 riboswitch
• RNA interference