The FDA approval of UF‘s AAV technology in voretigene neparvovec (Luxturna) for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy almost 4 years ago marked a turning point in gene therapy.

Since then, clinicians have witnessed the positive impact that gene therapy has had on the lives of patients and their families.

“Luxturna dramatically improves retinal sensitivity, resulting in improved night vision in most patients and even visual acuity in some patients,” said Mark Pennesi, MD, Ph.D., of the Casey Eye Institute Ophthalmic Genetic Clinic at Oregon Health & Science University in Portland, in an interview.

The Adeno-associated virus (AAV) is the “delivery vehicle” for gene therapy, but the AAV’s capsid, or protein shell, is what steers the virus to the target cells and tissues, such as the heart, kidneys, lungs, and brain. As part of the strategic research collaboration focused on optimized genetic capsid codes, AavantiBio and the University of Florida will implement advanced cellular, molecular, and computational tools to develop next-generation AAV gene therapies. By utilizing machine learning and UF’s HiPerGator 3.0 supercomputer, the company is seeking to optimize genetic codes to create a pipeline of improved capsids for more effective and safer delivery for gene therapy.

“We are thrilled to build upon our partnership with the University of Florida and strengthen our commitment to developing the safest and most effective gene therapies to help patients with rare genetic diseases,” said Bo Cumbo, president and chief executive officer of AavantiBio. “The smallest changes in the genetic code of gene therapy capsids have the potential to dramatically improve biodistribution and efficacy to targeted tissues. We look forward to pursuing this exciting research as we aim to build a sustainable platform approach beginning with our lead program in Friedreich’s Ataxia, and currently extending into other complex disease areas where there is a high unmet need.”

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That’s one of the questions the FDA is posing to its Cellular, Tissue, and Gene Therapies Advisory Committee as experts prepare for a two-day meeting Sept. 2-3, 2021. Depending on how the discussion goes — and what the agency makes of it — the results could completely redefine the rules for a major section of the booming gene therapy field: treatments that are delivered by adeno-associated virus vectors.

Coming in the shadow of preclinical red flags, safety alerts, clinical holds, and patient deaths, the meeting is designed to go through any and all toxicity risks related to AAV. And the FDA wants to get input on how it should deal with each of those issues, with regulatory implications on everything from mouse studies to clinical trials to manufacturing standards.

Advisory committee member Kenneth Berns of the University of Florida, one of the original researchers in AAV, has declared a conflict of interest due to grants or stock holdings in affected companies. He, along with Roland Herzog at Indiana University and Charles Vite at the University of Pennsylvania, were granted waivers to participate in the panel.

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Founded in 2015 based on the groundbreaking research of the late Mavis Agbandje-McKenna, Ph.D., a professor in the Biochemistry and Molecular Biology Department at the University of Florida, and Aravind Asokan, Ph.D., StrideBio, Inc., is a fully integrated gene therapy company focused on creating best-in-class genetic medicines with life-changing or curative potential for children and adults.

Proceeds will be used to advance Atsena’s ongoing Phase I/II clinical trial evaluating a gene therapy for patients with GUCY2D-associated Leber congenital amaurosis (LCA1), one of the most common causes of blindness in children, as well as complete manufacturing development for Phase 3. In addition, the funds will enable Atsena to expand its team to support the research and development of novel gene therapies, including the progression of two existing preclinical programs in inherited retinal diseases toward the clinic and advancement of the company’s innovative adeno-associated virus (AAV) technology platform.

“At Lacerta, we have dedicated our careers to the development of AAV gene therapy platforms and it remains our mission to advance these platforms and develop novel therapeutics for patients with neurodegenerative disorders,” said Dr. Edgardo Rodrίguez-Lebrón, president and chairman of the board at Lacerta. “We are looking forward to entering a new era, working in partnership with UCB. Our hope is that our combined expertise will lead to significant advances in identifying treatments for orphan CNS diseases.”

With its official move-in date on July 27, 2020, Lacerta Therapeutics is the newest tenant in Alachua’s Copeland Park. Strategically located in the heart of the University of Florida, Greater Gainesville and Alachua’s Research Cluster, Copeland Park offers state-of-the-art, build-to-suit laboratory and office space for biotechnology and life science companies.

Dr. Joe Reddy, president and chief executive officer of Lacerta Therapeutics, said, “Thanks to Brian Crawford and his team for delivering Lacerta’s customized facility in a timely manner, despite challenges due to COVID-19. This custom-built facility enables us to expand our team and continue our mission to make AAV-based therapies available for all patients with rare and serious neurological disorders. Soon, we plan to build a manufacturing facility on the adjoining lot to commercialize our proprietary, scalable OneBac AAV manufacturing platform.”

Its gene therapy program for X-linked retinitis pigmentosa (XLRP) is a case in point. By using its herpes-assisted vector expansion (HAVE) methodology, “we are now achieving finished product specifications that demonstrate nearly 90% full capsids with extremely low residuals, many of which fall below the level of detection, resulting in purity levels exceeding 97%,” said Dave Knop, Ph.D., head of process development at AGTC. “This is in addition to yields that are more than 10-fold higher than what we achieved in our Phase I/II manufacturing campaigns.” 

AGTC is a biotechnology company conducting human clinical trials of adeno-associated virus (AAV)-based gene therapies for the treatment of rare diseases.

Learn more about Ophthotech Expands Gene Therapy Pipeline in Orphan Retinal Diseases with Exclusive Option for Novel Product Candidates to Treat Best Vitelliform Macular Dystrophy (Best Disease).