Sam Berns is my friend. With the wisdom of a sage, he inspired me and many others about how to make the most of life. Suffered from a rare disease called progeriahis body aged at a rapid rate, and he died of heart disease at the age of 17, a brave life that was cut short.

My laboratory discovered the genetic cause of Sam’s disease two decades ago: Only one DNA letter was missing, a T that should have been a C in a critical gene called lamin A. The same misspelling is seen in nearly every 200 individuals around the world with progeria.

The opportunity to solve this disease by directly correcting the incorrect spelling of the relevant tissues of the body was only science fiction a few years ago. THEN Crispr arrived—the elegant enzymatic apparatus that allows the delivery of DNA scissors to a specific target in the genome. In December 2023, the FDA approves first Crispr-based therapy for sickle cell disease. That procedure requires taking bone marrow cells from the body, making a disabling cut of a particular gene that regulates fetal hemoglobin, treating the patient with chemotherapy to make room for the brain, and then again in the edited cells. A relief from lifelong anemia and severe pain attacks is now being given to sickle cell patients, albeit at a very high cost.

For progeria and thousands of other genetic diseases, there are two reasons why this same approach doesn’t work. First, the desired editing of most misspellings is not usually achieved by cutting the gene. Instead, correction is needed. In the case of progeria, the T that causes the disease must be edited back to a C. By analogy with a word processor, what is required is not “find and delete” (first generation Crispr), it is “find and replace” (next generation Crispr). Second, the wrong spelling should be corrected in the parts of the body most affected by the disease. While bone marrow cells, immune cells, and skin cells can be taken from the body to administer gene therapy, that doesn’t work if the primary problem is in the cardiovascular system (such as progeria) or the brain ( like many rare genetic diseases). In the lingo of the gene therapist, we need it ALIVE options.

The exciting news in 2025 is that both of these barriers are starting to come down. The next generation of Crispr-based gene editors, pioneered especially elegantly by David Liu of the Broad Institute, allows precise corrective edits of almost any misspelled gene, without prompting a scissor cut. As for delivery systems, the family of adeno-associated virus (AAV) vectors already provides the ability to achieve ALIVE editing in the eye, liver, and muscle, although more work remains to be done to optimize delivery to other tissues and ensure safety. Nonviral delivery systems such as lipid nanoparticles are in rapid development and may replace viral vectors in a few years.

Working with David Liu, mother of Sam Berns, and Leslie Gordon of the Progeria Research Foundation, my research group has already shown that an intravenous infusion of a ALIVE gene editor can greatly extend the lives of mice engineered to carry the human progeria mutation. Our team is currently working to bring it to a human clinical trial. We’re really excited about the potential for children with progeria, but that excitement may have a bigger impact. This strategy, if successful, could be a model for the approximately 7,000 genetic diseases where specific misspellings are known to cause the disease, but there is no therapy.

There are many obstacles, the cost is a major one that in a private investment is not for diseases that affect only a few hundred individuals. However, success for some rare diseases, supported by government and philanthropic funds, is likely to lead to efficiencies and economies that will help other applications in the future. This is the best hope for tens of millions of children and adults waiting for a cure. The rare disease community needs to move forward. That would have been what Sam Berns wanted.