The development of the corona vaccine can also lead to a gene therapy process for cancer

Researchers from Tel Aviv University led by Prof. Dan Farr succeeded in eliminating cancerous tumors from the inside using mRNA messenger RNA used to develop corona vaccines and instead of corona proteins they expressed CRISPR proteins that interrupted the tumor * So far the method has been successful in mice, but in an interview with the website Prof. Farr explains If humanity makes an effort, it is possible to shorten the arrival to Kalinka from a decade to two or three and save many lives

A significant step on the way to a cure for cancer: Researchers from Tel Aviv University have proven that the CRISPR system is also very effective in the treatment of metastatic cancer. The researchers developed an innovative technology - a transport system of new fat-based nanoparticles (CRISPR-LNPs), which carry the genetic messenger (messenger RNA) that codes for the Cas9 crisper enzyme specifically to the cancer cells and destroys it.

The revolutionary research was carried out in the laboratory of Prof. Dan Parr, the vice president for research and development and the head of the nanomedicine laboratory at the Shemunis School of Biomedical Research and Cancer Research, from the Center for Nanoscience and Nanotechnology, and the Center for Cancer Biology Research at Tel Aviv University. The research was conducted under the leadership of Dr. Daniel Rosenblum and PhD student Anna Gutkin, and with the assistance of other researchers from Prof. Parr's laboratory together with Dr. Dinora Friedman-Morbinski from the School of Biochemistry, Biophysics and Neurobiology at Tel Aviv University, Dr. Zvi Cohen, head of the Oncology Neurosurgery Unit At Sheba Hospital, Dr. Mark Bahlaki and his team from IDT in Iowa, USA and Prof. Judy Lieberman from Children's Hospital in Boston and Harvard University. The results of the groundbreaking research, funded by the Israel Cancer Research Fund (ICRF), are published today in the prestigious journal Science Advances.

Brain cancer and ovarian cancer

As part of the research, and to test the feasibility of the technology for cancer treatment, Prof. Parr and his team chose two of the deadliest tumors: brain cancer of the glioblastoma type and metastatic ovarian cancer. Glioblastoma is the most violent brain cancer, with most patients dying of the disease within 15 months of diagnosis, and only 3% surviving 5 years later.

The researchers demonstrated that by means of a single treatment with the CRISPR-LNPs it is possible to double the average life time and improve the survival of model mice with glioblastoma tumors by about 30%. 

Ovarian cancer is one of the leading causes of death among women, and the deadliest cancer of the female reproductive system. Most ovarian cancer patients are diagnosed in advanced stages of the disease, when the disease has already metastasized throughout the body. Despite the progress made in recent years, only about a third of patients will survive the severe disease. The treatment with CRISPR-LNPs in mice model of metastatic ovarian cancer improved the survival of the mice by 80%.

In an interview with the Hidan site, Prof. Parr explains: We have made good progress, although the distance to Kalinka is still great, but not very great. This is a study that has been going on for about five years, but before the Corona era, I thought that our chances of succeeding like we did now and reaching Kalinka would take maybe a decade.

mRNA technology has advanced a lot in the past year thanks to its use in the development of Moderna and Pfizer-Biontech's corona vaccines. We present another layer that is mechanistically more sophisticated but technologically intractable - I encode the CAS9 protein from the mRNA instead of the spike protein of the corona.

Even 3-4 years ago, stable mRNA could not be produced, it was very sensitive. Today we are able to stabilize the protein for 48 hours without it being damaged. Its level of expression has also improved thanks to sophisticated technologies of nucleic acid chemistry, and the ability to transfer it into the cell has also improved thanks to the helilipids that we and others are working on, which today completely disintegrate after bringing the drug into the cell, thus preventing damage.

You need courage, you have to take a risk and do it. The corona is an excellent example when there is no choice, people run forward and develop medicines and vaccines. We are in a revolution that will change the world of vaccines forever. When I started researching the field, in 2008 I said that in the future it would be possible to develop vaccines and cure people using mRNA. Everyone said it wouldn't happen, but in one year they developed processes that take 10-15 years. An mRNA vaccine is better than an attenuated or killed virus. If you take the number of experimenters who received the vaccine (without those who received the placebo) you reach 50 thousand, which is a respectable number, and no serious side effects were reported."

The first work in the world that demonstrated the ability to effectively and efficiently treat cancer in animals

"This is the first work in the world that has proven that it is possible to use the CRISPR system for effective cancer treatment in an intact animal with high efficiency," says Prof. Farr. "You have to understand that this is not chemotherapy. There are no side effects and there is no danger of a renewed outbreak of the cancer cell that underwent the treatment. The molecular scissors of the Cas9 cut the DNA of the cancer cell, disabled it and it is no longer able to replicate."

Prof. Parr adds: "The CRISPR system, which is capable of identifying and changing any genetic segment, has created a revolution in our ability to damage, repair and even replace genes in a personalized way. But compared to the extensive use of CRISPR in research, the clinical use is still in its infancy - since a safe and precise transport system is required that can only damage the target cells. The transport system we developed makes it possible to damage the DNA that allows the cancer cells to survive. This is an innovative treatment for aggressive types of cancer, which currently have no effective treatment."

The researchers note that the new study is the first demonstration of using the CRISPR system to treat these two aggressive cancers, but it opens up new opportunities for the treatment of other types of cancer, rare genetic diseases and chronic viral diseases such as AIDS. It should be noted that similar mRNA technology is used for corona vaccines by Moderna and Pizer (Biontech).

The next target is blood cancer

"We now want to continue experiments with blood cancers, which are very interesting from a genetic point of view, and with genetic diseases such as Duchenne muscular dystrophy," says Prof. Parr. "It will probably take more time to bring the new treatment to humans as well, but we are optimistic. This whole world of molecular drugs that activate messenger RNA (genetic messengers) is at its peak - as evidenced by the fact that most of the corona vaccines currently being worked on are based on this principle. When we talked about messenger RNA treatments 12 years ago, they thought it was science fiction. I believe that in the near future we will see many treatments based on genetic messengers for genetic diseases and cancer that are built on personalized medicine, and we are already working with international companies and foundations through Tel Aviv University's Ramot company to commercialize the technology to bring the news of genomic editing to humans."

Ramot Company, the application company of Tel Aviv University accompanies the researchers and registered patents on all these studies, but according to him, if you want to move forward quickly, you need to hand over the reins to industry. The researchers have already signed an agreement on one of the technologies of mRNA transport technology with Biotech, and are now seeking to commercialize the current research as well. According to Prof. Parr, pharmaceutical and biotechnology companies have already approached to be interested in the development.

At the conclusion of the interview with the scientist website, Prof. Parr explained: "There are two main challenges we faced - a technological challenge, a biological challenge. I think we have passed the technological challenge. The biological challenge depends on the type of tumor and what this specific person has, so we will have to sequence the genome of the specific patient and know which genes we will have to cut. In an ideal world I would also like to repair genes, but Crisper's efficiency in this task is still very low, but people are trying to improve that too. Many groups in industry and academia are working on improving the efficiency of CRISPR and I believe we will get there."

I would like to thank Daniel, Anna and a long line of researchers who worked hard, and also thank the Israeli Cancer Research Foundation, ICRN, for believing in and funding a dream that seems quite delusional. Before the Foundation, it was very difficult to promote science."

for the scientific article

More of the topic in Hayadan:

• The 2020 Nobel Prize in Chemistry was awarded to the scientists who developed the CRISPR "genetic numbers" immediately after the Wolf award
• A mysterious component in bacteria has been discovered as a last line of defense against viral infection
• The Innovation Authority approved the establishment of the CRISPR-IL consortium that combines artificial intelligence technologies to advance the field of genomic editing