What is nucleic acid medicine?

“Nucleic acid medicines” utilize “nucleic acid,” which refer to substances such as DNA and RNA that control genetic information, as drugs. These allow targeting of molecules such as mRNA and miRNA that cannot be targeted with traditional low molecular weight drugs and antibody medicines, and there is a great expectation for these drugs as next generation pharmaceuticals. Active research is being conducted globally as it is expected to lead to the creation of drugs which were previously intractable.

On the other hand, it has been pointed out that the development of nucleic acid medicines has issues to overcome, including “(i) instability of nucleic acid molecules in the body,” “(ii) concerns for adverse drug reactions,” and “(iii) difficulty in the drug delivery system (DDS).” Also, Japanese companies are steps behind in the development of nucleic acid medicines due to the monopolization of dominant patents of nucleic acid by companies in Europe and the US, causing interference with Japanese development.

Characteristics of nucleic acid medicines

“Nucleic acid medicine” is a next generation drug discovery technology with a completely different mechanism of action than traditional pharmaceutical products. It also features the ability to be manufactured easily at moderate sized molecules and the potential to exhibit efficacy and safety that surpasses those of antibody medicines. Due to these features, there is an expectation for nucleic acid medicines to be applied in cancer and hereditary disorders which were previously difficult to treat, as well as in illnesses such as influenza and viral infections.

Types of nucleic acid medicines

Nucleic acid medicines which utilizes DNA and RNA include those that target nucleic acids at the stage where protein is synthesized from genome DNA (such as mRNA and miRNA) and those that target protein.

Types and characteristics of nucleic acid medicines (drugs for prophylaxis and treatment)

There are nucleic acid medicines with different types and characteristics according to the targets and mechanisms of action.

Type Target Site of action Mechanism of action Summary
siRNA mRNA Inside the cell (cytoplasm) mRNA cleavage Double-stranded RNA with cleavage of mRNA homologous to the sequence (siRNA), single-stranded hairpin RNA (shRNA), etc. with effect according to the principle of RNAi
miRNA microRNA Inside the cell (cytoplasm) microRNA replacement Double-stranded RNA, miRNA of single-stranded hairpin RNA or its mimic is used to strengthen the function of miRNA deteriorated by disorders
Antisense mRNA、miRNA Inside the cell (in the nucleus, cytoplasm) mRNA and miRNA degradation, splicing inhibition Single-stranded RNA/DNA which binds to the target mRNA and miRNA to cause degradation or inhibition, or acts to skip exon when splicing
Aptamer Protein (extracellular protein) Outside the cell Functional inhibition Single-stranded RNA/DNA which binds to the target protein in a similar manner to antibodies/DNA
Decoy Protein (transcription factor) Inside the cell (in the nucleus) Transcription inhibition Double-stranded DNA with identical sequence to the binding site for transcription factor, which binds to the transcription factor of the affected gene to suppress the target gene
Ribozyme RNA Inside the cell (cytoplasm) RNA cleavage Single-stranded RNA with enzyme function for binding and cleavage of target RNA
CpG oligo Protein (receptor) Cell surface Immunopotentiation Oligodeoxynucleotide with CpG motif (single-stranded DNA)
Other - - - Nucleic acid medicines other than those listed above which act to activate innate immunity, such as PolyI:PolyC (double-stranded RNA) and antigen

Modified from "Report on Patent application technical trend survey Nucleic acids Medicine, March 2016"

Mechanism of siRNA silencing