Gene therapy at Saisei Mirai

Gene therapy for cancer is a cutting-edge treatment that works on the cause of cancer development. Gene therapy is a therapeutic method that reduces genetic abnormalities that cause cancer.

There are 2 Types of Gene Therapy

Immunotherapy may take 1-2 months to show its effect, but the feature of gene therapy is that it takes 2-3 weeks to show its effect. Other characteristics include almost no resistance (treatment becomes ineffective), and treatment is possible even if immunity is weakened by anticancer drugs or radiation therapy.

Characteristics of Cancer Gene Therapy

It is a treatment with few side effects because it does not damage normal cells. It is effective in combination with light and ultrasound dynamic therapy, immunotherapy, hyperthermia, chemotherapy, and radiation therapy, and, can be used in combination with high-dose IV vitamin C and low-dose naltrexone. It has a wide range of indications and can be used for most types of cancer. There is no age limitation, so anyone can use it.

Acquired gene mutations are the most common cause of cancer. They occur from damage to genes during a person’s life and they are not passed from parent to child. Cancer gene therapy is a type of treatment which uses normal genes to destroy cancer cells. The P53 tumor suppressor gene is the most frequently mutated gene in human cancer and more than 50% of all cancers involve a missing or damaged p53 gene. It affects G1-S phase arrest, G2-M phase arrest, along with DNA repair, when DNA damage is not severe.

The gene is usually taken into the cancer cell by a carrier called a vector. The most common types of carriers used in gene therapy are viruses. However, 5 years ago, we succeeded in producing new Liposomal P53 and PTEN gene therapy in Japan. We use 3 types of cationic liposomes as a vector instead of using a virus vector and that’s why the side effects of our gene therapy are so rare. So, gene therapy attempts to introduce genetic material (DNA or RNA) into living cancer cells to cause apoptosis. Liposomes are considered to be a novel drug delivery system and they could serve as tumor specific vehicles even without special targeting. This is because compared with normal capillaries, cancer capillaries have a disrupted endothelial lining which allows liposomes to better penetrate into cancer tissue.

Liposomal P53 Cancer Gene Therapy

Development Process of Cancer Cells and DNA Recovery:
How a Cancer Cell Develops

1. DNA gets damaged.
2. Transmission of RNA information is changed.
3. Prevention function for cellular growth will NOT work.
4. Tumor (cancer) suppressor gene (prevention of cancer) is lacking.
5. Cancer cells increase infinitely.
6. Cancer cells invade surrounding tissue.
7. Cancer cells invade veins.
8. Cancer transfers distance area of body through veins.
9. Cancer cells grow in distant area.
10. Primary tumor and metastases absorb nutrition.
11. It becomes terminal cancer.

DNA recovery

DNA of one cell consists of 3 billions bases.
Damage to DNA occurs from 50,000 to 500,000 times a day.
DNA recovery velocity and DNA damage velocity are related to each other.
If DNA recovery doesn’t reach DNA damage, the human body falls into the following:

• Ageing (cells get old) cells are in sleeping mode.
• Lack of apoptosis of cell (if cell damage is accumulated).
• Become cancerous (cells cannot be apoptosis and the transcription).

Apoptosis is a “trump card” which prevents cancer due to DNA damage.

A Novel Drug Delivery System

Liposomes could serve as tumor specific vehicles (even without special targeting).
Liposomes better penetrate into cancer tissue with disrupted endothelial lining.

Liposomes act as tumor-specific carriers.
The theory suggests that liposomes can better enter cancer tissue through the discontinuous
vascular endothelial cells of cancer.
In the picture above, the left one shows normal tissue, and the right one is cancerous tissue.
In the left, normal tissue, vascular endothelial cells are dense.
However, in the right picture of cancer tissue, vascular endothelial cells tend to break off.
Therefore, liposomes tended to be more likely to enter and accumulate in cancer.

P53 Guardian of the Genome

The P53 gene is commonly called the “guardian of the genome” because of its activities focused on maintaining genomic stability by surveying and repairing damaged DNA. Along with the Rb gene, it is very famous as a tumor suppressor gene. Cancer-free nematodes and even fruit flies have been confirmed to have the P53 gene. This P53 gene is also thought to be an important longevity assurance gene.

P53 and the Cell Cycle

The P53 tumor suppressor gene is the most frequently mutated gene in human cancer and more than 50% of all cancers involve a missing or damaged P53 gene.

The P53 tumor suppressor gene works by suspension of G1/S phase, G2/M phase, or repairing DNA if its damage is not large.

Liposome P53: New Cancer Gene Therapy

For the past 2 years, we have been developing and researching safe gene therapies. In particular, it is a type that does not use viruses.

Until now, cancer gene therapy used inactivated viruses as vectors, but our hospital has succeeded in developing a new type of gene therapy using liposomes. The goal is to reduce side effects, use more of the normal P53 gene, and increase efficacy.

Comparison Between Gendicine and Saisei P53 Gene Therapy

Let’s compare Gendicine, developed in China, and P53 gene therapy at our hospital. Gendicine was the world’s first gene therapy drug approved by the Chinese government. As a vector, they used Adenovirus. The gene therapy developed by our hospital uses cationic liposomes as vectors.

Gene dosage:
Gendicine is about 1 ng/vial.
The gene dosage of Saisei Mirai p53 gene therapy is 1 mg/1 vial, which is 1 million times more, compared to Gendicine.

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