Improving cell and gene therapy safety and performance using next-generation Nanoplasmid vectors

Adeno-Associated Virus Vectors in Clinical Trials

Adeno-Associated Virus: A Ubiquitous Commensal of Mammals

Development of a Web Course on Gene Therapy by the International Consortium of Gene Therapy

Expanded Opportunities for Methods and Clinical Development

Viral vector systems are crucial in delivering therapeutic genetic material for gene and cell therapy in clinical settings. With new progress in viral vector-based gene therapies, healthcare professionals and pharmacists must stay informed and apply appropriate biosafety precautions when handling these products. Comprehensive guidelines covering biosafety measures for every viral vector-based gene therapy, including storage, preparation, administration, and disposal, remain scarce. As viral vector-based gene therapy advances rapidly, it is critical to equip healthcare professionals with the expertise to safely manage these agents in a clinical setting. As gene therapies become more integrated into mainstream medicine, with 43 cell and gene therapy products approved as of 2025, pharmacists, nurses, and caregivers face new safety challenges when handling these therapies. While guidelines such as United States Pharmacopeia (USP) 797 and USP 800 provide a foundation for handling viral vector-based gene therapies, no single resource consolidates all biosafety considerations for healthcare professionals. This review provides an overview of the viral vector-based gene therapy landscape. It compiles best practices from various sources to establish a potential standardized approach to guide safe handling procedures for viral vector systems in a healthcare setting. By adopting the biosafety strategies outlined in this article, healthcare staff and pharmacists can safely manage viral vectors while developing standard operating procedures tailored to their specific clinical environments. Implementing these measures will support the continued advancement of gene therapy while ensuring the safety of healthcare providers, patients, and the environment.

Gene and Cell Therapy Funding Opportunities in Horizon 2020: An Overview for 2014–2015

1. Edward R.B. McCabe, MD, PhD* 1. 2. *Physician-in-Chief, Mattel Children’s Hospital at UCLA; Professor and Executive Chair, Department of Pediatrics, UCLA School of Medicine, Los Angeles, CA. Birth defects are the leading cause of infant mortality in the United States, representing more than 20% of all infant deaths. This infant mortality rate from birth defects exceeds that from sudden infant death syndrome, low-birthweight/short gestation, respiratory distress syndrome, and maternal complications. In addition, birth defects and genetic diseases represent major sources of morbidity for those who survive. As our ability increases to care effectively for those who have infectious diseases and other acute illnesses, individuals who have chronic illnesses due to genetic etiologies represent an increasing proportion of patients seen in the general pediatrician”s office. The Human Genome Project was initiated on October 1, 1990, and has a projected funding period of 15 years. The goal is to sequence the entire human genome, representing three billion base pairs that contain the coding sequences for approximately 75,000 genes. During the latter half of this century, investigations into the genetics of disease gathered increasing momentum. In addition to fundamental investigations into human genetics, technologic tools were developed that permitted large-scale genomic sequencing. These tools included the polymerase chain reaction (PCR), which permits amplification of hundreds of thousands or even millions of copies of DNA and requires only limited sequence data for its success; automated DNA sequencing, which allows increased sequence processing and decreased cost compared with manual methods; and improved information systems, which permit sophisticated analysis and assembly of the three billion base pairs of DNA in the human genome. Thus, the Human Genome Project represents the current chapter in our understanding, but it is neither the first nor the final chapter in this story. Once we know the sequences of all of the human genes, we must learn their functional roles in human development and disease pathogenesis. The Human Genome Project has been referred to as the “moon shot …

Efficacy and safety of gene therapy approaches for malignant gliomas: A systematic review and meta-analysis: ConNRNRNRNR22.5NRNR1011.413.511.9NRNRNR.

Self-complementary AAV Vectors; Advances and Applications

Elisa Manzotti speaks to Ying Cai, Nathalie Clement, Chantelle Gaskin, Matt Roach & Ashish Saksule. Ying Cai is the Sr. Director of Process Development at Ultragenyx Pharmaceutical. She heads AAV downstream process development and formulation development functions, also a CMC lead of AAV clinical programs. Prior to joining Ultragenyx, Ying worked at Sanofi, Biogen, Merck, and a few CDMOs. Ying has over 20 years’ experience in the development, validation, manufacturing and commercialization of different modalities including AAV, plasmid DNA, oligonucleotides, antibodies, antibody conjugates, and fusion proteins. Ying holds a Ph.D. in Chemical Engineering from the University of Arkansas at Fayetteville and a B.S. in Biochemical Engineering from Zhejiang University in China. Nathalie Clement has more than 25 years of experience in the field of Gene Therapy, with a strong expertise in viral vectors, specifically adeno-associated vectors, in the academic and industry settings. Her research focus has strongly been focused on optimizing processes to support large-scale production of high quality rAAV stocks and their implementation into the GMP settings. During her thesis work at the University Libre of Brussels, Belgium, she developed new recombinant viruses derived from the parvovirus Minute Virus of Mice (MVM) for cancer-selective gene therapy treatments. She then joined Dr. Michael Linden’s laboratory at Mount Sinai School of Medicine, New York, where she developed novel recombinant AAV vectors and directed the AAV Vector Core. She next joined the Powell Gene Therapy Center in 2008 as the Associate Director to supervise AAV production and testing at research, preclinical and clinical grades. She led the Process and Development Group and the Quality Control group responsible for the production and release of all AAV pre-clinical and clinical lots. During her time at UF she oversaw manufacturing, release and stability campaigns of more than 7 AAV INDs from start to finish, including CMC preparations and interactions with FDA. More recently, she spent several months at Resilience, Alachua, Florida, as the Director of Process and Development of the Viral Vaccines and Gene Therapy franchises. IN that role she oversaw viral vaccine and AAV production scales up to 200L in suspension format and in the icellis 500 platform for adherent platforms of a variety of viruses and AAV vectors. Currently Nathalie is taking a break before starting a new adventure in 2022. Chantelle Gaskin is a Field Applications Scientist, specializing in protein and viral vector purification and downstream process development. She held leadership positions at Applied Genetic Technology Corporation and Brammer Bio, prior to joining the Thermo Fisher Scientific Bioproduction Division in 2020. With over 10 years of experience in gene therapy, Chantelle has accumulated comprehensive knowledge of standard industry practices and regulatory standards, applying this knowledge to advance development of therapies for a variety of indications including ocular, CNS and systemic disease. Chantelle holds a Master’s degree in Chemistry from University of Florida and a Bachelor’s in Chemistry from Smith College. Matt Roach leads the AAV Process Development group at Precision BioSciences, which is focused on designing and implementing new strategies for the production and purification of adeno-associated virus. Matt completed his Bachelor’s degree in Biological Sciences at North Carolina State University and his Master’s degree in Microbiology and Cell Science at the University of Florida. Prior to Precision, Matt spent time at Pfizer working on the purification of AAV and the Biomanufacturing Training and Education Center training industry professionals on downstream bioprocessing operations. Ashish Saksule is the Cell and Gene Therapy process development lead and technical expert on bioprocessing platforms for viral vectors (Lentivirus and Adeno-associated virus vector) and non-viral vectors with more than 7 years of experience. Ashish has graduate degree in Chemical Engineering from Michigan Tech University, and Biotechnology graduate degree from Harvard University. His experience spans research & drug development, clinical stage and CRO/CMO settings. Ashish is currently working at Takeda within Global Gene Therapy and have previously worked at MilliporeSigma and Miltenyi Biotec.

Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting motor and non-motor functions. In advanced or treatment-resistant cases, surgical strategies such as deep brain stimulation (DBS) and MR-guided focused ultrasound (MRgFUS) offer substantial symptomatic relief. With recent progress in neurotechnology, biomedical engineering, and molecular therapies, new surgical approaches are emerging. This narrative review explores the future of PD surgical treatment over the next 5 to 10 years, focusing on innovative and potentially disease-modifying strategies.Method: A narrative literature review was conducted across PubMed, Scopus, and Embase, selecting recent clinical trials, systematic reviews, and experimental studies. Keywords used: “Parkinson’s Disease”, “DBS”, “focused ultrasound”, “gene therapy”, “cell therapy”, “brain-computer interface”, “neurotechnology”, “future perspectives”. Articles were included based on relevance, innovation, and clinical applicability. Data were organized by thematic categories. No statistical analysis was applied.Results: DBS remains the gold standard, reducing motor fluctuations and medication dependency. Its use in earlier disease stages is gaining support. MRgFUS provides a non-invasive lesioning option, though it is irreversible. Technological advances such as adaptive DBS, directional leads, cortical recordings (ECoG), and multi-target stimulation increase therapeutic precision. 7-Tesla MRI and tractography enable stimulation of symptom-specific networks. BCIs and spinal neuroprostheses are under investigation for gait restoration and freezing control. In biological domains, gene therapies using viral vectors (AAV-GDNF, AADC, GAD) show neuroprotective effects. Optogenetics and chemogenetics (DREADD) allow remote control of neural circuits. iPSC-based cell therapies have demonstrated safety in early-phase trials. Gene correction (e.g., GBA1, LRRK2) and anti alpha-synuclein antibodies represent promising future strategies. Discussion: The field is shifting from symptomatic treatment to personalized, disease-modifying neurosurgical approaches. Integration of neuromodulation with biotechnology may alter disease trajectory. Adaptive DBS and multitarget designs optimize stimulation, while gene and cell therapies offer restoration of affected networks. However, high costs, device complexity, safety concerns, and ethical issues in placebo-controlled trials remain obstacles.Conclusions: Over the next 5 to 10 years, surgical care in PD is expected to evolve into a multimodal and individualized model, combining neurostimulation, biological therapies, and digital interfaces. These strategies aim not only to manage symptoms, but also to slow or modify disease progression, improving long-term autonomy and quality of life.

Strategies to Modulate Immune Responses: A New Frontier for Gene Therapy

Investigational new drugs submitted to the Food and Drug Administration that are placed on clinical hold: the experience of the Office of Cellular, Tissue and Gene Therapy

After an injury, axons in the central nervous system do not regenerate over large distances and permanently lose their connections to the brain. Two promising approaches to correct this condition are cell and gene therapies. In the present work, we evaluated the neuroprotective and neuroregenerative potential of pigment epithelium-derived factor (PEDF) gene therapy alone and combined with human mesenchymal stem cell (hMSC) therapy after optic nerve injury by analysis of retinal ganglion cell survival and axonal outgrowth. Overexpression of PEDF by intravitreal delivery of AAV2 vector significantly increased Tuj1-positive cells survival and modulated FGF-2, IL-1ß, Iba-1, and GFAP immunostaining in the ganglion cell layer (GCL) at 4 weeks after optic nerve crush, although it could not promote axonal outgrowth. The combination of AAV2.PEDF and hMSC therapy showed a higher number of Tuj1-positive cells and a pronounced axonal outgrowth than unimodal therapy after optic nerve crush. In summary, our results highlight a synergistic effect of combined gene and cell therapy relevant for future therapeutic interventions regarding optic nerve injury.

Optogenetics: Controlling Cardiac Depolarization and Hyperpolarization Using Combined Cell and Gene Therapy and Light-Sensitive Proteins