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Sam Berns was a friend of mine. With the wisdom of a wise man, he inspired me and many others on how to get the most out of life. Patients with rare diseases called progeriahis body aged very quickly, and he died of heart failure when he was only 17 years old, his brave life was too short.
My lab discovered the cause of Sam’s disease two decades ago: A single DNA letter went wrong, a T that should have been a C in a critical gene called lamin A. The same misspelling is found in nearly every 200 people in the world. the world is progeria.
The possibility of curing the disease by correcting the wrong expression in the right body was just a scientific myth a few years ago. So Crispr He discovered—a beautiful enzymatic tool that allows DNA to be sheared to a specific region of the genome. In December 2023, a The FDA approved the first treatment for Crispr for sickle cell disease. This involved removing bone marrow cells from the body, creating a specific gene that controls the fetus’s hemoglobin, giving it medical treatment to find a place in the bone marrow, and then reimplanting the transplanted cells. Relief from lifelong anemia and chronic pain is now being offered to sickle cell patients, albeit at a high cost.
For progeria and thousands of other genetic diseases, there are two reasons why the same approach may not work. First, the desired change in most transcription factors will not be achieved by inhibiting gene transcription. Instead, improvement is needed. In the case of progeria, the T that causes the disease needs to be changed back to C. Compared to a word processor, what is needed is not “find and delete” (Crispr of the first generation), but “find and change” (next generation Crispr) . Second, the wrong words must be corrected in the parts of the body that have been severely damaged by the disease. Although bone marrow cells, immune cells, and skin cells can be removed from the body to provide gene therapy, this may not work when the underlying problem is in the cardiovascular system (such as progeria) or the brain (as is often the case .genetic diseases). According to the gene therapist, we need it life options.
The good news in 2025 is that all these barriers are starting to come down. The next generation of Crispr-based gene editors, brilliantly pioneered by David Liu of the Broad Institute, allow precise editing of almost any defective gene, without having to cut it with scissors. As for delivery systems, the family of adeno-associated virus (AAV) vectors already offers the possibility of implementation. life changes in the eyes, liver, and muscles, although there is a lot of work to be done in order to improve the transfer to other products and ensure safety. Non-viral delivery systems such as lipid nanoparticles are in rapid development and may be able to repel viruses within a few years.
Working with David Liu, the mother of Sam Berns, and Leslie Gordon of the Progeria Research Foundation, my research team has already shown that one intravenous infusion. life gene editors can greatly extend the lifespan of mice that have been engineered to be genetically modified. Our team is now working on bringing this to human clinical trials. We are very excited about the possibilities for children with progeria, but that excitement can have a far-reaching impact. This approach, if successful, could be an example of about 7,000 diseases of this type where the wrong transcription that causes the disease is known, but no treatment is available.
There are many obstacles, the cost is high because private funds are not available for diseases that affect only a few hundred people. However, the success of a few rare diseases, with the help of the government and human resources, can create an efficient and economic system that will help with other projects in the future. This is the best hope for tens of millions of children and adults who are waiting for a cure. The rare disease category should continue. This is what Sam Berns would have wanted.
