Disruptive Dozen | World Medical Innovation Forum - Gene and Cell Therapy

2022 Disruptive Dozen

The 12 Most Disruptive Technologies

The ”Disruptive Dozen” results from interviews of one hundred Mass General Brigham senior Harvard faculty followed by a rigorous selection process to identify the twelve mostly likely to have significant impact on healthcare.

Mass General Brigham
Press Release

#12 | Reawakening the X Chromosome: A Therapeutic Strategy for Devastating Neurodevelopmental Diseases

Jeannie Lee, MD, PhD

Molecular Biologist, MGH; Professor of Genetics, HMS

The biology of the X chromosome, one of two sex-determining chromosomes in humans, is unique. Females carry two copies of the X chromosome, yet one copy is randomly selected for inactivation in cells throughout the body. This unusual biology could hold the key to much-needed treatments for a group of rare yet devastating neurodevelopmental disorders, which predominantly affect females. Scientists are devising a strategy to reawaken the dormant X chromosome, an approach that could yield effective treatments for these serious disorders.

#11 | Engineering Cancer-Killing Cells that Target Solid Tumors

Khalid Shah, PhD

Vice Chairman of Research, Department of Neurosurgery, BWH; Professor, HMS

Despite great leaps in cancer treatment, solid tumors remain the most challenging tumors to treat, in part due to the hostile environment in which they grow, which suppresses the immune system. Now, scientists are devising innovative cell therapies that promise to open new therapeutic opportunities for solid tumors. One approach involves making CAR-T cells more like computers, using simple logic to decide which cells are cancer and which are not. Another involves creating therapeutic tumor cells that have dual properties — killing cancer cells and modulating the immune system.

#10 | New Technologies for Delivering Gene Therapies

Natalie Artzi, PhD

Assistant Professor of Medicine, HMS

Viruses have been co-opted as delivery vehicles, shuttling therapeutic genes to cells in the body. But this method isn’t ideal and comes with some significant drawbacks. Now, researchers are exploring new ways of delivering gene therapies. These include miniature needles that can penetrate the skin with minimal pain and discomfort, and an implantable, biodegradable device that can provide localized, sustained release of therapeutics. These novel delivery methods could help expand the reach of gene therapy.

#9 | Regrowing Cells in the Inner Ear to Treat Hearing Loss

Zheng-Yi Chen, DPhil

Associate Scientist, Eaton-Peabody Laboratories, Mass Eye and Ear; Associate Professor of Otolaryngology Head and Neck Surgery, HMS

Healthy hearing requires specialized cells in the inner ear called hair cells, which perform critical sensory functions, converting mechanical signals from sound into electrical signals that travel to the brain. If the cells are damaged or lost, which often happens with age or after repeated exposure to loud sounds, the body cannot repair them. But researchers have discovered a potential workaround that can stimulate existing cells in the ear to be converted and give rise to new hair cells. This novel regenerative approach could offer hope to millions of patients who suffer from hearing loss.

#8 | CAR-T Cell Therapies Take Aim at Autoimmune Diseases

Matt Frigault, MD

Clinical Director, Cellular Immunotherapy Program, MGH; Assistant Professor of Medicine, HMS

The immune system is designed to protect the body from pathogens and other foreign invaders by differentiating “self” from “non-self.” When it mistakenly targets its own cells and tissues, autoimmune diseases can emerge. While some treatments are available, they often involve general suppression of the immune system — a blunt-edged approach that can leave patients vulnerable to life-threatening infections. Now, scientists are exploring potential treatments that involve CAR-T cells — patients’ own immune cells that are rewired to give them new, powerful therapeutic properties.

#7 | On the Move: Cell Therapies to Restore Gut Motility

Allan Goldstein, MD

Chief of Pediatric Surgery, MGH, Surgeon-in-Chief, MassGeneral for Children; Marshall K. Bartlett Professor of Surgery, HMS

The human body has a second brain, known as the enteric nervous system, which controls the movement of food through the digestive tract. But when the neurons associated with this system are missing or injured, gut motility can be impaired. Effective treatments are deeply needed; in many cases, surgery is the only option. Now, scientists are developing an innovative cell replacement therapy — which harnesses patients’ own cells and converts them into enteric neurons — that could treat gut motility disorders.

#6 | A Flexible, Programmable Approach to Fighting Viruses

Galit Alter, PhD

Principal Investigator, Ragon Institute, MGH; Professor of Medicine, HMS

Scientists are developing a novel form of anti-viral therapy that can be programmed to target a range of different viruses — from well-known human pathogens, such as hepatitis C, to those less familiar, such as the novel coronavirus SARS-CoV-2. This new approach to fighting viral infections harnesses a popular family of gene editing tools, known as CRISPR-Cas. While these tools have gained attention for their capacity to modify human genes, their original purpose in nature was to defend bacteria from viral infections. As a throwback to these early roots, scientists are now adapting CRISPR tools to tackle a variety of viruses that infect humans.

#5 | Realizing the Promise of Gene Therapy for Brain Disorders

Fengfeng Bei, PhD

Principal Investigator, Department of Neurosurgery, BWH; Assistant Professor of Neurosurgery, HMS

Gaining access to the brain with gene therapies has proven a major challenge. A commonly-used vehicle for gene therapy — a virus called AAV — cannot readily access the brain when injected into the bloodstream because it cannot penetrate a major biological roadblock, known as the blood-brain barrier. Now, scientists are engineering new versions of AAV that can cross the blood-brain barrier and sidestep potential toxicities associated with AAV-based gene therapy. These molecular feats represent a significant step toward safe, effective gene therapies for a range of neurological conditions.

#4 | Harnessing the Power of RNA to Treat Brain Cancer

Anna Krichevsky, PhD

Associate Professor of Neurology, BWH

Scientists are tapping the potential of RNA, the close chemical cousin of DNA, to create potent new therapies for a range of diseases, including a devastating form of brain cancer called glioblastoma. This cancer is notoriously difficult to treat and highly adaptable, overcoming practically every treatment that’s so far been deployed against it. Most patients die within a year to 18 months of diagnosis. But now, new approaches that either target RNA or mimic its activity could offer a critical toehold in destroying this aggressive cancer.

#3 | Cell Therapies to Conquer Common Forms of Blindness

Michael Gilmore, PhD

Chief Scientific Officer, Mass Eye and Ear; Sir William Osler Professor of Ophthalmology, HMS

Cell therapy represents a promising new area of treatment for common forms of blindness. Rather than fixing the genetic causes of a particular disease, these therapies offer a functional cure by replacing critical cells that have been lost or injured. A variety of cell therapy approaches are now under development that seek to replenish cells that are important for healthy vision — for example, in the retina, the specialized structure critical for light-sensing, and in the cornea, the clear covering that helps bend and focus light as it enters the eye.

#2 | A Gene Editing Solution to Increase the Supply of Donor Organs

James Markmann, MD, PhD

Chief, Division of Transplant Surgery, MGH; Claude E. Welch Professor of Surgery, HMS

There is a critical shortage of donor organs for life-saving transplants. One way to address this crisis involves harvesting organs from animals and placing them into human patients. The concept, called xenotransplantation, has only recently become feasible due to advances in gene editing technologies, which make it possible to molecularly engineer organs from animals, such as pigs, that can sidestep the human immune system. Researchers are making significant strides in developing animal organs that are suitable for humans and recently embarked on the first in-human transplants of gene-edited pig organs.

#1 | Restoring Sight by Mending Broken Genes

Demetrios Vavvas, MD, PhD

Associate Director Retina Service, Mass Eye and Ear; Solman and Libe Friedman Professor of Ophthalmology, Co-Director Ocular Regenerative Medical Institute, HMS

Scientists are testing a new form of gene therapy that could help overcome some of the challenges of conventional approaches, which rely on viruses to add new, healthy copies of genes into cells. Instead of replacing defective genes, the new method repairs them, like a word processor edits misspelled words. The method, known as CRISPR-Cas-9 gene editing, could open the door to treating genetic forms of vision loss that are not suited to conventional gene therapy — as well as a host of other medical conditions.