Business & Technology

Application to nucleic acid therapeutics

In September 2020, NanoCarrier merged with AccuRna, Inc. which conducts research to achieve practical use of nucleic acid therapeutics, including using micellar nanoparticles as carriers for nucleic acid therapeutics.
Through this merger, NanoCarrier acquired a nucleic acid therapeutics pipeline based on new value in addition to its existing small molecule cancer drugs pipeline.

Nucleic acid therapeutics

Nucleic acid therapeutics act with high specificity on intracellular molecules which cannot be targeted by low molecular weight drugs or antibody drugs.

Nucleic acid therapeutics are expected to offer groundbreaking therapies for cancer and genetic diseases but their stability in the blood is seen as an issue. AccuRna’s DDS technology improves in-vivo stability and increases the efficacy of nucleic acid therapeutics and can be expected to reduce the burden of treatment for the patient.

 Nucleic acid therapeutics is a generic term for therapeutics based on nucleic acids, which can be broadly divided into oligonucleotide therapeutics created by chemical synthesis and and mRNA produced by a transcription process. The term is sometimes used in a narrow sense to refer to oligonucleotide therapeutics only, however, for the purposes of this explanation the term “nucleic acid therapeutics” refers collectively to both oligonucleotide therapeutics and mRNA. The main feature of nucleic acid therapeutics is that they can target a wide range of intracellular molecules which low molecular and antibody drugs cannot reach. Because of their high target specificity, nucleic acid therapeutics also demonstrate outstanding efficacy and safety and are the focus of many research and development projects being conducted around the world to develop groundbreaking therapies for cancer and genetic diseases.

The current status and future of nucleic acid therapeutics

 Prior to 2014, only three nucleic acid therapeutics were approved for use in Japan, the United States and Europe. However, over the course of five years from 2016, a further nine products were approved and, with more than 100 products in the development pipeline, nucleic acid therapeutics are attracting a great deal of attention. This interest was triggered by the success of SPINRAZA, a treatment for spinal muscular atrophy (SMA) which was developed by IONIS and launched in 2016. The condition of patients with this progressive, genetic, neuromuscular disorder, who usually do not live beyond two years, improved significantly when administered SPINRAZA twice a year, causing a huge stir.

 A major contributor to progress in the development of nucleic acid therapeutics was nucleic acid modification technology. Usually, when administered in vivo, nucleic acids are immediately degraded by nucleases. Chemical modifications of nucleic acids made it possible to increase resistance to digestion by nucleases, enabling nucleic acids to be used as therapeutics. The next problem was how to reach the site of disease for intracellular drug delivery. The technology which overcomes this problem is drug delivery system (DDS) technology.

Unit Polyion Complex (uPIC) technology is an extremely efficient delivery technology in the sense that it successfully delivers small interfering RNA (siRNA) and antisense oligonucleotide (ASO) to the tumor site. It also protects mRNA, which lacks stability in the blood stream, from degrading enzymes, enabling highly efficient and sustainable protein expression.

Commercial potential (diseases/markets)

The size of the market for nucleic acid therapeutics was extremely small prior to 2016 but suddenly expanded with the emergence of SPINRAZA in 2016 and, with a total of eight products approved in 2019 and at 19% CAGR, market size is predicted to exceed 700 billion yen at its peak in 2025 (according to a survey by Seed Planning, Inc.). Many of the nucleic acid therapeutics currently in phase III trials are being developed not only in the now mainstream domain of genetic and rare diseases but also in the cardiovascular domain which represents an even bigger market, and, based on the success rate, the size of market is expected to reach 520 billion yen (10 products) in 2025. Furthermore, based on products which are currently in phase I or phase II trials, further growth is forecast and the global nucleic acid therapeutics market size is likely to exceed 2 trillion yen in 2030. Thus, nucleic acid therapeutics can be said to be firmly establishing themselves as a third drug modality after low molecular and antibody drugs, and the outlook is positive.

Categories of nucleic acid therapeutics

Categories of nucleic acid therapeutics are as follows:

Antisense oligonucleotides (ASOs)

Single-stranded DNA or RNA sequences which bind to their target RNA sequence inside the cells and impair mRNA translation into protein. Some act by binding to the splice sites in genes and blocking splicing.

siRNA

Double-stranded RNA molecules which slice their target mRNA within cells with high specificity, inhibiting gene expression.

Aptamers

Single-stranded DNA or RNA sequences which, due to the three-dimensional structure of their molecules, bind to and inactivate proteins and other complex molecules with high specificity.

Decoys

Double-stranded DNA molecules which bind to transcription factors inside the cells and inhibit expression of the genes regulated by these transcription factors.

mRNA

RNA with base sequence information and a structure that can be translated to build a protein is artificially synthesized and delivered into cells to build the intended protein. Attempts are being made to apply mRNA in vaccines against infectious diseases such as COVID-19 and cancer vaccines.

We are pushing ahead with research into DDS for nucleic acid medicines using siRNA, ASO, and mRNA. Our aim is to promote unprecedented innovation in nucleic acid-based therapies for conditions such as breast cancer and glioblastoma and to make therapies that lessen the patient burden available quickly.