Top 12 Disruptive Gene and Cell Therapy Technologies Announced
Cholesterol-lowering therapies, treatments for common blood disorders, and genome editing tools make the list of breakthroughs
Mass General Brigham today announced its selections for the sixth annual “Disruptive Dozen,” 12 emerging gene and cell therapy (GCT) technologies with the greatest potential to impact health care in the next few years. The technologies were featured as part of the World Medical Innovation Forum held virtually from Boston to examine GCT’s potential to impact patient care including a range of diseases and health system opportunities.
The 2021 Mass General Brigham Disruptive Dozen are:
- A new generation of cholesterol-lowering therapies
Researchers have pinpointed key genes involved in cholesterol and lipid metabolism that represent promising targets for new cholesterol-lowering treatments. Instead of disabling a disease-related protein, gene-silencing therapies prevent the protein from being made at all. That durability means patients could receive an injection of a gene-silencing drug every six months to control their blood cholesterol. Another transformative genetic medicine can alter the instructions written in a particular gene. Known as CRISPR base editing, this technology offers precision and potential permanence: patients may be able to undergo a one-time treatment and maintain healthy cholesterol levels for a lifetime.
- A genetic fix for two common blood disorders
Currently, devastating diseases such as sickle-cell disease and beta-thalessemia can only be cured by a bone marrow transplant, which can be risky and not feasible due to the lack of suitable donors. Now, new genome editors — tools that make precise changes to a person’s DNA — are paving the way toward a different kind of cure. One approach uses a type of genome editing called CRISPR, and involves reactivating fetal hemoglobin, which can substitute for the missing or faulty adult version in these diseases. This CRISPR-based gene therapy is now being tested in clinical trials and early results are encouraging. Other gene therapies are also in the works, including those based on older technologies that augment rather than repair defective genes.
- A new class of genome-editing tools
Genome editing technologies are having a significant impact across biomedicine, especially on the field of gene therapy. Despite their precision and ease of use, these tools cannot fix every genetic mutation, including those that change a single genetic base, similar to a one-letter misspelling on a page. More than 30,000 point mutations in the human genome are known to cause disease. Thanks to a new class of genome-editing tools, known as base editors, it is feasible to correct some of these so-called point mutations. The first base-editing therapies are now under development for a range of human diseases including sickle cell disease, inherited blindness, and genetic forms of high cholesterol. As base editing technologies continue to mature, researchers are also working to apply it to more common diseases, such as Alzheimer’s disease.
- Moving beyond viruses to ferry genes
The first gene therapies to reach the clinic use viruses which have been molecularly honed and tailored to allow for the safe, effective delivery of human genes. While these viruses can transfer genes into cells — a requirement for gene therapy — they are not a perfect solution. Now, as scientists seek to build next-generation gene therapies, they are pursuing alternatives for gene delivery. These include highly sophisticated bubbles fashioned from nanoparticles, which help protect and direct gene therapies to their intended destination within the body. If gene therapies can be targeted more precisely to specific organs or tissues, they could be used to treat a broader range of disorders. These efforts are boosted by the recent development of a pair of highly effective coronavirus vaccines that use lipid-based nanoparticles to deliver their therapeutic cargo.
- Mobilizing bone marrow stem cells
Some life-saving therapies, including certain forms of gene therapy, depend on bone marrow stem cells. But these cells are not easily accessible, and the protocol is long and can cause pain, nausea, and other complications. Scientists are developing a new approach that promises to streamline this process and help reduce the barriers that can hinder the delivery of some gene therapies. This new method holds promise not only for bone marrow transplantation, but also for gene therapies that depend on manipulating bone marrow stem cells. These treatments — known broadly as ex vivo gene therapy — require isolating bone marrow stem cells, treating the cells outside of the body with gene therapy, and then infusing the modified cells back into patients’ bloodstream.
- Expanding gene therapy’s reach for eyes and ears
One of the first gene therapies approved in the U.S. treats a rare genetic form of blindness with a one-time injection into the eye. Its success is paving the way for many other eye gene therapies that are now under development. Some 200 genes in humans are directly linked to vision problems, underscoring the incredible potential of the technology. Scientists are also pursuing novel gene therapies for another critical sensory organ, the ear. With more than 150 genes tied to hearing loss and deafness, there is a great need for treatments that can help protect and restore hearing. Millions of people in the U.S. suffer from hearing loss, yet there are currently no FDA-approved medicines to treat it. Unlike the eye, the inner ear is difficult to reach with therapeutics. To help overcome this hurdle, scientists have fine-tuned the molecular make-up of the viruses used in gene therapy to create versions that can penetrate the ear’s internal structures.
- Groundbreaking cell therapy for Parkinson’s disease
Approximately 10 million people worldwide suffer from Parkinson’s disease, a chronic condition that stems from the progressive loss of dopamine-producing neurons in the brain, which help control movement. Unfortunately, there is no available drug that protects or stops the neurons from dying. But scientists and clinicians are developing a revolutionary approach to replace these lost neurons, harnessing stem cell-based methods to convert patients’ own blood cells into dopamine-producing neurons. Although this cell therapy does not fix the root causes of Parkinson’s disease, it could provide a functional cure by replacing the dopamine-producing neurons in patients’ brains and restoring normal movement to their bodies.
- Stem cell therapies for diabetes
Type 1 diabetes affects over a million people in the U.S. Patients must keep track of their blood sugar levels and inject themselves periodically with insulin, all because the cells in their own bodies that supply the hormone have been destroyed by the immune system. Scientists are working on a novel cell-based treatment for type 1 diabetes that involves replacing these lost insulin-producing cells with a special laboratory-grown variety. Over the last several years, scientists have developed several formulas for generating these cells using different stem cells as the key ingredient, along with cloaking strategies and efforts to enable replacement cells to release their own immune-blocking signals. As these technologies continue to advance toward the clinic, researchers hope to bring them to bear on another disease: type 2 diabetes. Worldwide there are over 400 million people with type 2 diabetes, many require insulin injections, underscoring the need for a more durable solution.
- The next wave of CAR-T-cell therapies
CAR-T therapy is a groundbreaking form of gene and cell therapy in which a patient’s own immune cells are isolated, genetically rewired in the laboratory with certain therapeutic properties, and then infused back into the bloodstream. For difficult to treat blood cancers, CAR-T therapies have proven remarkably effective, with some patients living for years cancer-free. Researchers are now working to expand the reach of this transformative technology by simplifying cell production and manufacturing and applying the approach to other disease areas. Scientists are also creating off-the-shelf versions of CAR-T therapies, selecting from an assortment of pre-made options for an immunological match for a patient. This could help expand the number of patients who could receive CAR-T therapies and minimize the time between doctors prescribing the treatment and patients receiving it. There are also efforts underway to broaden the diseases that CAR-T therapies can treat, including development of CAR-T therapies that can kill solid tumors or target entirely new areas, like autoimmune disease.
- Improving gene therapy through designer viruses
A virus found in nature has become a workhorse of gene therapy. Known as adeno-associated virus, or AAV, it is a popular choice among gene therapy developers because of its long track record and overall safety. But it’s not a perfect solution. That’s why scientists are working to create designer AAVs in the laboratory that address some of the virus’ shortcomings. The work promises to expand the clinical impact of gene therapy by broadening the number of patients and diseases that can benefit. Using data-driven methods, scientists are modifying the molecular make-up of the viruses to generate enhanced versions that home to specific organs, like the lung and kidney, which are not targeted by the current slate of therapeutic AAVs. Researchers are also fine-tuning AAVs to infect some cells in a tissue but not others — for example, a specific subtype of neurons in the brain. Finally, efforts are underway to create AAVs that can evade detection by the immune system, which would help expand the clinical impact of gene therapy by making more patients eligible to receive it.
- Antisense Oligonucleotides: A novel therapeutic platform for neurodegenerative disease
Some gene therapies seek to repair or replace what’s been lost, like genes that are abnormally silent because of a genetic misspelling that terminates their usual function. But other genes can be broken in a different way that gives them new, often unexpected behaviors. To address these wayward genes, scientists have devised a class of innovative gene therapies called antisense oligonucleotides, or ASOs. They are designed with biochemical precision to shut down the activity of a target gene at its molecular roots and hold promise for neurodegenerative diseases. ASOs are relatively straightforward to engineer, so they can often be designed more quickly than other therapies. Over the last four years, six new ASO drugs were approved by the FDA, and many more are under development for a range of conditions, including neurodegenerative diseases such as ALS, Huntington’s disease, and Alzheimer’s disease.
- New gene and cell therapies to fight glioblastoma
Glioblastoma is the most common type of brain cancer in adults, and, tragically, most patients die within a year to 18 months of diagnosis. Now, using a variety of approaches — from cancer-killing viruses to rewired immune cells to even cancer cells themselves — researchers are working to develop a slate of innovative treatments with the power to eradicate glioblastoma tumors and give patients longer, cancer-free lives. One approach involves cancer-killing viruses, engineered in the laboratory to seek and destroy tumors. Researchers are also applying CAR-T cell technology, in which patients’ own immune cells are isolated, molecularly rewired with therapeutic powers, and then put back in the body. Another novel cell therapy builds on a remarkable, decade-old discovery: cancer cells that spread within the body can find their way back to their original tumor. This re-homing is spurring efforts to genetically engineer patients’ own tumor cells to endow them with cancer-killing properties. Once the cells are placed back into the body, they can return home and destroy their counterparts.
For detailed information on each of the Disruptive Dozen technologies, including video updates, please visit https://worldmedicalinnovation.org/2021-disruptive-dozen/
About Mass General Brigham
Mass General Brigham is an integrated academic healthcare system, uniting great minds in medicine to make life-changing impact for patients in our communities and people around the world. Mass General Brigham connects a full continuum of care across a system of academic medical centers, community and specialty hospitals, a health insurance plan, physician networks, community health centers, home care, and long-term care services. Mass General Brigham is a non-profit organization that is committed to patient care, research, teaching, and service to the community. In addition, Mass General Brigham is one of the nation’s leading biomedical research organizations and a principal teaching affiliate of Harvard Medical School. For more information, please visit massgeneralbrigham.org.
About Mass General Brigham Innovation
Innovation is the 150-person business development unit of Mass General Brigham responsible for the worldwide commercial application of the unique capabilities and discoveries of Mass General Brigham's 74,000 employees. Innovation supports the research requirements of its 6,200 Harvard Medical School faculty and research hospitals. It has responsibility for industry collaborations, venture investing, international consulting, licensing, innovation management, company creation, technology marketing, open innovation alliances, and workforce development. Its annual World Medial Innovation Forum is underway virtually May 19-21.
Mass General Brigham: