First Look | World Medical Innovation Forum - Gene and Cell Therapy

First Look

Realizing GCT Therapies

Mass General Brigham investigators presented their high potential new technologies. Clinicians and researchers from Harvard-affiliated hospitals highlighted the potential of their research in a up-close looks at new technologies. 

These showcased technologies are designed to inform investors, entrepreneurs, investigators, donors and others who share a passion for accelerating the application of high impact technologies to the benefit of patients.

2021 Presenters

Versatile Polymer-Based Nanocarriers for Targeted Therapy and Immunomodulation
Enhancing Vesicles for Therapeutic Delivery of Bioproducts
Personalized iPSC-Derived Dopamine Progenitor Cells for Parkinson’s Disease
Oncolytic Viruses: Turning Pathogens into Anticancer Agents
Gene Therapies for Neurological Disorders: Insights from Motor Neuron Disorders
Rare but Mighty: Scaling Up Success in Single Gene Disorders
Unlocking the Secret Lives of Proteins in Health and Disease
New Scientific and Clinical Developments for Autologous Stem Cell Therapy for Parkinson’s Disease Patients
Impacts of Human Genetic Variation on CRISPR Gene Editor Off-Target Effects
Treating Rett Syndrome through X-Reactivation
Enhanced Gene Delivery and Immunoevasion of AAV Vectors without Capsid Modification
Cell Therapy Innovations at MGH
Gene Therapy for Cerebral Genetic Vasculopathies
RNA Therapy for Brain Cancer
Regenerating T Cell Immunity
Getting to the Heart of the Matter: Curing Genetic Cardiomyopathy
Repurposed Tumor Cells as Killers and Immunomodulators for Cancer Therapy
Control of AAV Pharmacology by Rational Capsid Design
Versatile Polymer-Based Nanocarriers for Targeted Therapy and Immunomodulation
Natalie Artzi, PhD

Assistant Professor, BWH
nartzi@partners.org

Dr. Artzi uses an integrative approach that combines material science, chemistry, imaging and biology in the design of smart materials. In her latest work, looking at non-viral vectors for gene therapy, she has developed a nanoparticle-based platform that allows the delivery of different types of nucleic acids. In animal models, this platform has demonstrated efficacy in multiple therapeutic areas.

Enhancing Vesicles for Therapeutic Delivery of Bioproducts
Xandra Breakefield, PhD

Geneticist, MGH; Professor, Neurology, HMS
breakefield@helix.mgh.harvard.edu

Koen Breyne, PhD

Molecular Biologist, MGH; Instructor, Neurology, HMS

Drs. Breakefield and Breyne have been focused on developing non-viral vectors to enhance gene delivery and have identified extracellular vesicles as a promising payload carrier for therapeutic interventions. They have advanced their work, developing what they term “supercharged extracellular vesicles,” a universal delivery technology applicable to functional delivery of multiple biomolecules, and are working to translate this to the clinic.

Personalized iPSC-Derived Dopamine Progenitor Cells for Parkinson’s Disease
Bob Carter, MD, PhD

Chairman, Department of Neurosurgery, MGH; William and Elizabeth Sweet, Professor of Neurosurgery, HMS
bcarter@mgh.harvard.edu

A prolific researcher, Dr. Carter’s latest work has focused on developing a treatment for Parkinson’s disease. His efforts have resulted in a number of innovations in the development of induced pluripotent stem cells-derived dopamine progenitor cells. Dr. Carter and his team have successfully treated 1 patient and are working studies to support a full Phase 1 trial.

Oncolytic Viruses: Turning Pathogens into Anticancer Agents
Nino Chiocca, MD, PhD

Neurosurgeon-in-Chief and Chairman, Neurosurgery, BWH; Harvey W. Cushing Professor of Neurosurgery, HMS
eachiocca@partners.org

A pioneer in biologic treatments of central nervous system disorders, Dr. Chiocca will discuss his latest efforts where he uses oncolytic viruses to treat solid tumors. He has completed a Phase 1 trial with a first generation oncolytic HSV to treat glioblastoma and is now working on IND-enabling studies for second-generation therapeutic. Beyond glioblastoma, this technology is applicable to pancreatic cancer and many other solid tumors.

Gene Therapies for Neurological Disorders: Insights from Motor Neuron Disorders
Merit Cudkowicz, MD

Chief of Neurology, MGH
mcudkowicz@partners.org

A leading researcher in amyotrophic lateral sclerosis, Dr. Cudkowicz will discuss recent developments in gene therapy to treat ALS and other neuron disorders. Her innovative work in efficient clinical trial design has further boosted the impact of these drug development programs.

Rare but Mighty: Scaling Up Success in Single Gene Disorders
Florian Eichler, MD

Director, Center for Rare Neurological Diseases, MGH; Associate Professor, Neurology, HMS
feichler@partners.org

An expert in neurodegenerative disorders, Dr. Eichler’s work focuses on combining biological insights, concurrent biomarker development and natural history studies to accelerate progress in advancing treatments for single gene disorders. Dr. Eichler has used this approach to scale up success in identifying treatments for several rare disorders that are currently in or advancing toward the clinic.

Unlocking the Secret Lives of Proteins in Health and Disease
Anna Greka, MD, PhD

Associate Professor, Medicine, BWH; Associate Professor, Medicine, HMS
agreka@bwh.harvard.edu

Dr. Greka’s work focuses on the fundamental aspects of cell membrane protein biology, complementing this work with tools from molecular biology, genomics, proteomics, and chemical biology. Using this approach, she made a key discovery by studying a proteinopathy in the kidney. Lessons learned from this work have implications for a diversity of toxic proteinopathies well beyond the kidney.

New Scientific and Clinical Developments for Autologous Stem Cell Therapy for Parkinson’s Disease Patients
Penelope Hallett, PhD

NRL, McLean; Assistant Professor of Psychiatry, HMS
phallett@mclean.harvard.edu

Dr. Hallett has been instrumental in advancing stem cell therapy for Parkinson’s disease. She will discuss progress in developing autologous stem cell transplantation to replace dopamine neurons. This treatment effectively repopulated lost dopaminergic synapses and restored function in nonhuman primates. She is now working on pre-IND studies aimed at reaching the clinic two years.

Impacts of Human Genetic Variation on CRISPR Gene Editor Off-Target Effects
J. Keith Joung, MD, PhD

Robert B. Colvin, MD Endowed Chair in Pathology & Pathologist, MGH; Professor of Pathology, HMS
jjoung@partners.org

A leading innovator in gene editing, Dr. Joung has co-founded multiple biotechs. He will discuss his latest work in understanding the magnitude and impacts of off-target edits, an important challenge for therapeutic use of CRISPR technologies. His group has developed a highly sensitive method to identify true off-target sites.

Treating Rett Syndrome through X-Reactivation
Jeannie Lee, MD, PhD

Molecular Biologist, MGH; Professor of Genetics, HMS
lee@molbio.mgh.harvard.edu

Dr. Lee specializes in the study of epigenetic regulation by long noncoding RNAs and uses Xchromosome inactivation as a model system. She is now leveraging this work to develop a treatment for Rhett Syndrome by reactivating the healthy allele on the inactive X- chromosome. Animal models have shown that even a modest reactivation can result in significant improvements.

Enhanced Gene Delivery and Immunoevasion of AAV Vectors without Capsid Modification
Casey Maguire, PhD

Associate Professor of Neurology, MGH & HMS
cmaguire@partners.org

Dr. Maguire’s work focuses on developing better gene therapy vectors. His lab discovered a new gene delivery system that addresses three key challenges with current AAV vectors. Dr. Maguire has taken this finding of “enveloped AAVs” and is working to develop it into a broader technology platform for clinical application.

Cell Therapy Innovations at MGH
Marcela Maus, MD, PhD

Director, Cellular Immunotherapy, Cancer Center, MGH; Associate Professor, HMS
mvmaus@mgh.harvard.edu

Dr. Maus’s work is at the forefront of next generation CAR T approaches that overcome some of the limitations of current therapies. Her rational-design approach to developing cell therapies for specific diseases has dramatically accelerated the bench to patient development timeline. As a result, she has developed a strong pipeline of therapeutic candidates for a number of oncology indications that are currently in or about to enter clinical testing.

Gene Therapy for Cerebral Genetic Vasculopathies
Patricia Musolino, MD, PhD

Co-Director Pediatric Cerebrovascular Service, MGH; Assistant Professor of Neurology, HMS
pmusolino@partners.org

Dr. Musolino will discuss her work developing treatments for cerebral genetic vasculopathies, a condition that can lead to progressive white matter degeneration and recurrent strokes. Preliminary work editing the disease-causing mutation shows high efficiency on restoring sequence and functional phenotype, and is progressing toward pre-clinical proof-of-concept.

RNA Therapy for Brain Cancer
Pierpaolo Peruzzi, MD, PhD

Neurosurgery, BWH; Assistant Professor of Neurosurgery, HMS
pperuzzi@partners.org

Dr. Peruzzi will discuss his research employing microRNA in a novel method to co-opt the molecular machinery of glioblastoma cells in a way that made them more vulnerable to treatment. He is now working to develop this into a microRNA gene therapy platform, that is versatile, can be used with any microRNA, and can be used with current delivery vectors. He expects the technology to reach the clinic in 2-3 years.

Regenerating T Cell Immunity
David Scadden, MD

Director, Center for Regenerative Medicine; Co-Director, Harvard Stem Cell Institute, Director, Hematologic Malignancies & Experimental Hematology, MGH; Jordan Professor of Medicine, HMS
david_scadden@harvard.edu

A recognized leader in regenerative medicine and co-founder of several companies, Dr. Scadden is currently working on regenerating T cell immunity. He has identified and validated two complementary approaches that increased formation of T cells as well as the diversity of the new T cells. The next steps include testing in non-human primates and development of clinical scale processes.

Getting to the Heart of the Matter: Curing Genetic Cardiomyopathy
Christine Seidman, MD

Director, Cardiovascular Genetics Center, BWH; Smith Professor of Medicine & Genetics, HMS
cseidman@genetics.med.harvard.edu

A pioneer in the discovery of the genetic basis for heart muscle disorders, Dr. Seidman’s latest research is focused on developing treatments to cure two forms of genetic cardiomyopathies. Combining her insights with molecular strategies to specifically modulate gene expression provide the ability to silence or correct mutant genes and boost healthy gene expression in patients with two forms of genetic cardiomyopathy.

Repurposed Tumor Cells as Killers and Immunomodulators for Cancer Therapy
Khalid Shah, PhD

Vice Chair, Neurogurgery Research, BWH; Director, Center for Stem Cell Therapeutics and Imaging, HMS
kshah@bwh.harvard.edu

Dr. Shah has led pioneering efforts in cell therapy and understanding basic cancer biology. His current work exploits tumor cell “self-homing” to return to the main tumor site. This behavior is combined with CRISPR edited bi-functional autologous tumor cells to deliver the therapeutic payload directly to the tumor.

Control of AAV Pharmacology by Rational Capsid Design
Luk Vandenberghe, PhD

Grousbeck Family Chair in Gene Therapy, MEE; Associate Professor, Ophthalmology, HMS
luk_vandenberghe@meei.harvard.edu

A co-founder of multiple companies including Akouos and Affinia, Dr. Vandenberghe is a leader AAV gene therapy. Recognizing the limitations inherent in AAV technology, he successfully developed an approach toward rational design of AAV vectors for translationally relevant properties. Having successfully seen multiple therapeutic candidates developed using this approach advance to the clinic, Dr. Vandenberghe is looking beyond to further improving the cost and manufacturing of AAV vectors.