Microscopic image shows a mouse cochlea treated with a viral vector developed by Dr. Jeffrey Holt.
Pioneers Deliver on the Promise of Nature’s Medicine Chest
There’s a revolution underway in medicine. Scientists are turning to nature and engineering new treatments—biologics—to mimic the intricacies of life itself.
But what are they, exactly?
Unlike conventional chemically synthesized medicines, biologics are derived directly from natural molecules and offer precise disease targeting and a potentially lower risk of unforeseen side effects.
While big pharmaceutical companies excel in later-stage clinical and manufacturing development, biologics require the dedication and tenacity during early discovery found in academic labs, a sweet spot for Boston Children’s. “It’s a unique strength for us,” says Executive Vice President and Chief Scientific Officer Nancy Andrews, MD, PhD, “as these innovations can evolve from our laboratories to clinical practice and, eventually, to commercialization.”
Meet three scientists harnessing the building blocks of biology to unlock groundbreaking interventions.
Revolutionizing Treatments for Genetic Hearing Loss
For the millions of patients affected by hearing loss and deafness, the only available treatments are devices like hearing aids or cochlear implants. While these interventions can be beneficial, they don’t work in every case and fall short of replicating natural hearing.
Jeffrey Holt, PhD, and his team have explored multiple gene therapy approaches and demonstrated they can restore hearing in mouse models of three forms of human genetic hearing loss. What sets their efforts apart is the seamless interaction between laboratory research and clinical practice. They’re engineering mice with genetic mutations similar to humans and generating patient-derived stem cells to grow inner ear tissue, an approach that offers valuable tools for controlled testing and validating potential treatments. Thanks to essential support from donors like Jeffrey Barber and Kimberly Hsu-Barber, Dr. Holt’s work could transform the landscape of genetic hearing loss therapies, offering new possibilities for patients to experience a world filled with sound.
“Knocking Down” Disease through RNA Interference
Imagine genes as instruction manuals that contain directions for making essential proteins for the body’s many functions. RNA interference (RNAi), a natural process cells use to regulate the activity of genes, utilizes small pieces of RNA to interfere with the gene’s instructions, knocking down protein production.
Judy Lieberman, MD, PhD, was the first to demonstrate that RNAi could be harnessed in animal models to target specific genes involved in medical conditions. First, she showed RNAi could save mice from a fatal form of hepatitis and later successfully blocked HIV transmission in mouse models. This critical work paved the way for RNAi drug development to treat everything from rare genetic diseases to common conditions like high cholesterol.
Now, Dr. Lieberman is aiming to advance the commercialization of RNAi-based therapies for cancer. She developed strategies to target cancer cells by knocking down genes essential for cell division and manipulating genes involved in the immune response to control and potentially eliminate the tumor. A major benefit of this approach is the ability to create cocktails of small RNAs targeting multiple genes, addressing resistance issues common in single-drug treatments. Dr. Lieberman’s research shows the immense potential of biologics, opening doors to a new era of targeted therapies.
Building a Better Vaccine
Richard Malley, MD, has been on a mission throughout his career to develop more effective and less expensive vaccines against diseases that claim the lives of millions of children around the world. Modern vaccine production is extensively intricate, costly and complex. Dr. Malley and his Boston Children’s col-leagues, Yingjie Lu, PhD, and Fan Zhang, PhD, created a highly efficient vaccine technology platform, Multiple Antigen Presenting System (or MAPS), to target a broad range of infectious diseases. (See image below to learn how MAPS works.)
With early support from critical funders, including the Bill & Melinda Gates Foundation, they formed a biotech company, Affinivax, which applied MAPS technology to bring new vaccines to market. In one of Boston Children’s most successful intellectual property deals, Affinivax was recently acquired by GSK. As GSK advances clinical trials for pneumococcal vaccines and other diseases, Dr. Malley’s group is currently working on applying their platform to more pathogens, including Salmonella, Shigella, Group B streptococcus and tuberculosis. They are collaborating closely with GSK to expedite the development of additional vaccines, amplifying the global impact of this work.
Picture a pathogen, like the pneumococcus bacterium, as a peanut M&M. The candy shell protects the virus from the body’s defenses. The MAPS technology acts like a molecular glue, binding the surface sugars (the shell) with pathogen-related proteins. This precise and virtually irreversible binding ensures the immune system can efficiently recognize and respond to the pathogen, leading to a robust immune response.
