The Vector
Volume 10, Issue 8: August 2021
Editorial Team
Edith Pfister, Ph.D. – Editor, The Vector
Karen Bulaklak, Ph.D. – Associate Editor, The Vector
Jon Brudvig, Ph.D. – Junior Editor, The Vector
Inside This Issue
Leadership Message
Breaking Through
From Molecular Therapy
Society News
Career Center
Public Policy
Industry News
Leadership Message
Register Now for the 2021 Policy Summit
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Hello ASGCT Members,
I hope you’re all doing well! First off, I would like to congratulate everyone involved in the efforts behind ASGCT’s Patient Education Program, which just won a national award! ASGCT was named a winner of the 2021 “Power of A” Silver Award from the American Society of Association Executives (ASAE) for the program. The Patient Education program launched in 2018 with the goal of making accurate, reliable and accessible information about gene and cell therapies available to patients and the public. The program has grown every year to provide resources for patients and families dealing with rare diseases, and I’m so proud of its impact! Congratulations to each one of our committee volunteers, staff, patient advocacy partners, consultants, and sponsors for the success of the program.
Registration is now open for the 2021 Policy Summit, a hybrid event September 22-24 that will be held in person at the JW Marriott Washington, DC and virtually. We’re excited to welcome keynote speaker Andi Lipstein Fristedt, FDA deputy commissioner for policy, legislation, and international affairs, who will speak about key issues in regulatory policy. Other sessions are on accelerated approval, AAV vector integration, Medicaid coverage and reimbursement, and more, which you can review here. Register now to secure your spot, as there is limited in-person seating. If you’re planning to attend in person, make sure to book your hotel and travel arrangements soon. To comply with Washington, D.C.’s requirement and the CDC’s recommendations, ASGCT will require all individuals to wear masks in indoor public spaces during the meeting regardless of vaccination status. You can visit this section of the website to learn more about how we’re working to keep attendees safe during the event.
Tomorrow, August 13, we will host a free Professional Development Café on grant writing. On August 18, we’re holding another free event, an AAV Integration Roundtable, where experts will discuss the status of AAV integration research. Come learn more about the current state of knowledge of AAV integration from preclinical and clinical studies, and what we hope to learn from future research to guide the safe implementation of AAV gene therapies.
Finally, the call for abstracts is now open through August 31 for the 2021 International Oncolytic Virus Conference (IOVC)! Registration will open later this month for what is currently planned as a hybrid event in Sedona, AZ. Also open through August 31 is the window to apply for ASGCT’s Mentorship Award Program. An initiative of our Diversity & Inclusion Committee, the program will award $5,000 plus research costs to five graduate students or postdoctoral fellows for a mentored summer research project in 2022. Read the details here and apply!
I hope you’ll take advantage of these opportunities and pass them along to other potential members in your networks, and enjoy the waning days of summer.
Stay safe!
Beverly L. Davidson, PhD
ASGCT President
Breaking Through
Implication of miRNAs Alternative: MicroRNAs in Extracellular Vesicles of Educated Stem Cells Attenuate Brain Inflammation
Markoutsa E, Mayilsamy K, Gulick D, Mohapatra SS, Mohapatra S
DOI: https://doi.org/10.1016/j.ymthe.2021.08.008
Summary by Karen Bulaklak, PhD
Inflammation is a defining trait of age-related neurodegenerative disorders, such as Alzheimer’s disease (AD). In AD, amyloid β oligomers (AβOs) and tau oligomers trigger the endogenous inflammatory response, which is meant to repair damage, yet works to drive pathology. In a recent paper by Markoutsa et al, the group looked to mesenchymal stem cells (MSCs) for combating neuroinflammation. MSCs have anti-inflammatory qualities; however, the exact mechanism is unknown. One hypothesis is that MSCs secrete extracellular vesicles (EVs), which can work as delivery vehicles as part of the cells’ secretome, carrying cargo to neighboring cells to exert a therapeutic effect. To better understand how MSCs function therapeutically, the research group looked at the inflammatory microenvironment and characterized EVs produced under these circumstances.
Activated microglia are a known source of pro-inflammatory cytokines and reactive oxygen species (ROS) in the brain and participate in creating chronic neuroinflammation. The research group looked at the effect of the MSC secretome in either the soluble or EV form on LPS-challenged microglia. They found that the EV fraction significantly reduced expression of proinflammatory cytokines TNF-α, IL-6, and IL-1β and ROS production. These microglia also showed less Iba-1 staining, which is consistent with a resting phenotype. To determine if activated MSCs, or “edu-MSCs,” produced more effective EVs, the conditioned media from either LPS- or AβO-challenged microglia cells was added to MSCs. The secretome of these edu-MSCs was then analyzed, which confirmed the presence of EVs. These edu-MSC-derived EVs were added to activated microglia, and analysis showed that cytokine expression and activated phenotype was further reduced compared to unstimulated MSCs. To test efficacy in an in vitro AD model microenvironment, AβOs were used to activate microglia for several days. After addition of AβO-stimulated edu-MSC EVs, proinflammatory cytokine expression, ROS, and activation markers were significantly reduced. Next, the edu-MSC-derived EVs were administered intranasally to a an LPS-treated mouse model to recapitulate brain inflammation, as well as a mouse model of AD. Reduced levels of inflammatory markers and normalized morphology were observed in the brains of edu-MSC EV-treated mice compared to the MSC EV-treated group. Furthermore, decreased amyloid deposition was found in the brains. Interestingly, edu-MSCs also improved performance in tests for memory, motor activity, and anxiety-like behavior. Finally, to understand the mechanism of edu-MSC EVs, their miRNA cargo was analyzed and compared to MSC EVs. These analyses showed that four of the top overexpressed miRNAs within edu-MSC EVs targeted critical genes in the TLR4 signaling pathway. They also found that upregulated miRNAs were involved in neurogenesis and generation of neurons. These results thus elucidated a pathway in which MSCs exert their anti-inflammatory and therapeutic functions.
In summary, Markoutsa et al uncovered an underappreciated therapeutic mechanism utilized by MSCs. Not only can this help to improve MSC-based treatments, but it also provides inspiration for EV-based delivery into the brain. With further understanding of natural mechanisms, we can one day hope to create better therapies for neurodegenerative diseases.
From Molecular Therapy
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This month, read the latest issue of Molecular Therapy. On the Cover: The cover image presents an artistic view of how the ginger-derived exosome-like nanoparticles (GELNs, yellow) inhibit SARS-CoV-2 (cyan)-mediated lung inflammation.
Catch up on the most recent issues of other journals in the Molecular Therapy family:
Molecular Therapy: Methods & Clinical Development
Molecular Therapy: Oncolytics
Molecular Therapy: Nucleic Acids
You can view calls for papers and other announcements from Molecular Therapy here.
Society News
Patient Education Wins National Award, Releases New Resources
ASGCT has been named a winner of the 2021 "Power of A" Silver Award from the American Society of Association Executives (ASAE) for our Patient Education Program! In the last month, the program has also released two new resource modules. Check out our page on GM1 Gangliosidosis (GM1), a rare genetic disorder caused by a mutation to the GLB1 gene, which instructs cells to produce an enzyme that breaks down fats and sugars in the lysosomes. We also released a page highlighting red flags that could indicate a stem cell therapy or trial has not received the required regulatory review.
Upcoming Events and Deadlines
Career Center
Are you looking for a job in the field of gene and cell therapy? Check out the new ASGCT Career Center for great opportunities with industry, government, and academic organizations. Sign up to receive alerts for open jobs in your area.
If you're from a recruiting institution, advertise in the Featured Jobs section to target the 4,000+ audience of The Vector.
Featured Jobs
Public Policy
ASGCT Impacts Strategic Planning Process for National Institutes of Health
ASGCT has made an impact on the strategic plans, and thus the future direction, of two Institutes of the National Institutes of Health (NIH). This achievement became clear with the publication of the National Eye Institute’s (NEI) 2021 Draft Strategic Plan and the 2021-2026 Final Strategic Plan for the National Institute of Neurological Disorders and Stroke (NINDS). A key strategic priority for the Society is to support continued innovation by encouraging federal research funding for gene and cell therapy, so it was encouraging to see gene and cell therapies given prominent support in NINDS’ final and NEI’s draft strategic plans. Several of ASGCT’s specific suggestions were also incorporated into each plan. To read more about the Society’s recommendations, check out the ASGCT news blog.
Newborn Screening Programs Expand with ASGCT Support
After advocacy from a coalition of organizations including ASGCT and led by the EveryLife Foundation, new laws were passed in Georgia and Ohio to better ensure their state newborn screening (NBS) programs stay up to date with new additions to the federal Recommended Uniform Screening Panel (RUSP). Both states now require their NBS programs to expeditiously consider screening for any condition that is added to the RUSP, while Ohio also added SMA and X-linked adrenoleukodystrophy to their NBS panel. ASGCT will continue to support efforts to ensure patients can access genetic screening and testing as one of its core patient access priorities.
RMIP Funding Opportunity Announced
NIH and a collection of its Institutes and Centers, in coordination with the Food and Drug Administration (FDA), has published a funding opportunity announcement (FOA) as part of the Regenerative Medicine Innovation Project. The FOA is seeking clinical trial applications to explore and enable the development of safe and effective regenerative medicine interventions using adult stem cells; letters of intent are due September 2, 2021. ASGCT has supported RMIP and other focused federal funding streams to enable continued innovation in the gene and cell therapy field, particularly for translational research and early-stage clinical trials.
Industry News
- Sarepta Acquires Investigational Gene Therapy for LGMD2A
- Gilead's Kite bets on early-stage biotech to advance allogeneic cell therapies
- BioNTech Completes Acquisition of Kite’s Neoantigen TCR Cell Therapy R&D Platform and Manufacturing Facility in Gaithersburg, Maryland
- FDA allows Novartis gene therapy trials to resume after nearly 2 year pause
- EXCLUSIVE Sanofi offers to buy U.S. biotech, mRNA partner Translate Bio -sources
- FDA Puts APB-102 Gene Therapy for SOD1 ALS on Fast Track
- Sorrento Receives FDA Authorization to Start Phase 1 Clinical Trial of Proprietary, "Off-the-Shelf", Allogeneic anti-CD38 DAR-T (Dimeric Antigen Receptor-T) Cell Therapy to Treat Relapsed or Refractory Multiple Myeloma
- Astellas to pay Minovia $20M upfront, with $420M on the table per product, for mitochondrial cell therapies
- Alnylam and PeptiDream Enter into Collaboration Agreement to Discover and Develop Peptide-siRNA Conjugates for Targeted Delivery of RNAi Therapeutics to a Broader Range of Extrahepatic Tissues
- bluebird bio and National Resilience Ink Cell Therapy Strategic Alliance
- Eye problems in more patients spells end of Adverum’s DME gene therapy program
- Bluebird, with little fanfare, is first to bring a second gene therapy to market
- Mirimus, Inc. Forms Strategic Collaboration with Biogen (BIIB) to Develop RNAi-Based Therapeutics for Neurological Disease Indications
- AavantiBio and Aldevron Announce Strategic Partnership to Develop Next Generation Gene Therapies for Rare Genetic Diseases
- First patient dosed in optogenetic gene therapy trial
- GSK's Planned UK Biotech and Life Sciences Hub to Create 5,000 Jobs
- Seattle biotech startup Sana Biotechnology will develop 163K square-foot facility in the Bay Area
- Poseida joins Cellares’ early-access cell therapy tech program
- Caribou Biosciences Announces Dosing of First Patient in Phase 1 Clinical Trial Evaluating CB-010, a CRISPR-Edited Allogeneic Anti-CD19 CAR-T Cell Therapy, in Patients with Relapsed or Refractory B Cell Non-Hodgkin Lymphoma
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