What is a Gene?

The blueprint of our bodies is described by approximately 20,000 genes, which are encoded by 3 billion DNA units lined up with four types of bases (A, G, T, C). Our bodies, which began as fertilized eggs, are made up of around 200 different types of cells, all of which are created through the division of a single cell. Regardless of their type, such as muscle, eye, or blood cell, they all have exactly the same genetic sequence.

So, if they all have the same blueprint, why do they end up with different forms and functions?

This is because there are switches on every 20,000 genes, and these switches control when, where and how much they should be turned on. For example, in liver cells, genes characteristic of the liver are turned on, and in eye cells, genes characteristic of the eye are turned on, and the proteins encoded in each DNA are created. It’s like an orchestra, where it’s decided which instruments will play and when, and at what volume, and by strictly controlling these switches, the body maintains its functions and expresses its diversity. However, if this harmony is disrupted, you will become ill.

Gene Therapy Approaches

There are various approaches to gene therapy. The CRISPR-GNDM® technology , a proprietary epigenome editing technology that our company has developed, control the ON/OFF switch of the target gene without involving the double-stranded cleavage of the DNA sequence, and is a highly scalable approach that has the potential to develop safer therapeutic drugs for various genetic diseases.

・ Gene replacement: A method of introducing and replacing a normal gene for a gene that has errors or defects
・ siRNA/antisense oligo: A method in which nucleic acids injected from the outside act on genes with errors or defects, temporarily preventing the production of proteins with dysfunctional or abnormal functions

Delivery Method

In gene therapy, it is necessary to deliver genes to the cells where the disease is occurring. This is done using what are called “carriers”, or viral vectors. Viruses have the property of easily invading human cells, so this property is used to deliver the necessary genes into the cells. There are two methods of actual treatment

– Ex vivo method
This method involves removing cells from the body, introducing the gene outside the body, and then returning the cells to the body. For example, this method is used when introducing genes into bone marrow cells.

– In vivo method
For cells that cannot be removed, such as nerves and muscles, the virus vector is injected directly into the body. The genes delivered reach the target cells and begin to work properly.

In recent years, tissue-specific viral vectors have been developed that can introduce genes with higher selectivity for target cells, and this has made it possible to reduce the toxicity that occurs in off-target cells and to increase the amount delivered to the target cells.

US Approved Gene Therapies

Gene therapies approved in the US (as of end 2024)

Since 2017, more than 10 gene therapies have been approved by the FDA, and the number is increasing every year. In addition, there are currently more than 1,500 gene therapies under development and clinical trials globally, and gene therapy is continuing to grow as a new modality in pharmaceutical development.

Brand Approved in Indication Developed by Patient population
LUXTURNA 2017 Inherited Retinal Dystrophy Spark/Roche 2 per 100,000
ZOLGENSMA 2019 SMA* (Avexis)/Novartis 1 in 10,000 live births
(Approx. 10,000 to 25,000 in US）
HEMGNIX 2022 Haemophilia B uniQure/CSL Behring 1 in 30,000 male
Adstiladrin High-Risk Bladder Cancer Ferring Pharmaceuticals 70,000 to 80,000 people per year in America
Vyjuvek 2023 DEB* Krystal 3.5〜20.4 in 1,000,000
ROCTAVIAN Haemophilia A BioMarin 1 in 5,000 male
Cagsevy SCD CRISPR Tx/Vertex 100,000 in America
LYFGENIA Bluebird
Lenmeldy 2024 Metachromatic Leukodystrophy Orchard/KyowaKirin 1 in 100,000 live births
beqvez Haemophilia B pfizer 1 in 30,000 male
ELEVYDYS DMD* Sarepta 1 in 3,500 male birth

SMA: Spinal muscular atrophy; DEB: Dystrophic epidermolysis bullosa; DMD: Duchenne muscular dystrophy