A new study reports the findings of the functional evaluation of six AAV vectors in 12 preclinical models of the human liver. The study, which aimed to uncover which combination of models is the most relevant for the identification of an AAV capsid variant for safe and efficient gene therapy to primary human hepatocytes, is published in Human Gene Therapy.
Leszek Lisowski, from The University of Sydney, and co-authors, note that robust, biologically- and clinically-predictive preclinical models of the safety and efficacy of liver-targeted AAV-based gene therapy are lacking. The investigators compared AAV-based gene transfer efficiency targeting the liver in 12 frequently used preclinical models, including in vitro models, such as hepatic cell lines, human-induced pluripotent stem cell (hiPSC)-derived hepatocytes, and adult stem cell-derived hepaltic organoids.
They focused primarily on ex vivo models, such as 2D and 3D primary non-human primates (NHP) and human hepatocytes cultures, and in vivo models, including murine and human hepatocytes in xenograft mice and NHPs.
“Even though a perfectly predictive preclinical model does not exist, our study shows that each model provides a unique insight into the vector function,” stated the investigators.
“Based on our results and the fact that each model brings a unique perspective that adds to the overall functional evaluation of AAV vectors, we propose that multiple models should be used to paint a more complete picture and help us make the most informed decision as to which vector should be used in each clinical application.”
“This study represents a highly innovative approach to combining data from multiple different experimental systems into an overall predictive model,” says Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Chan Medical School.
More information: Adrian Westhaus et al, Assessment of Pre-Clinical Liver Models Based on Their Ability to Predict the Liver-Tropism of Adeno-Associated Virus Vectors, Human Gene Therapy (2023). DOI: 10.1089/hum.2022.188
PackGene is a CRO & CDMO technology company that specializes in packaging recombinant adeno-associated virus (rAAV) vectors. Since its establishment in 2014, PackGene has been a leader in the AAV vector CRO service field, providing tens of thousands of custom batches of AAV samples to customers in over 20 countries. PackGene offers a one-stop CMC solution for the early development, pre-clinical development, clinical trials, and drug approval of rAAV vector drugs for cell and gene therapy (CGT) companies that is fast, cost-effective, high-quality, and scalable. Additionally, the company provides compliant services for the GMP-scale production of AAVs and plasmids for pharmaceutical companies, utilizing five technology platforms, including the π-Alpha™ 293 cell AAV high-yield platform and the π-Omega™ plasmid high-yield platform. PackGene’s mission is to make gene therapy affordable and accelerate the launch of innovative gene drugs. The company aims to simplify the challenging aspects of gene therapy development and industrialization processes and provide stable, efficient, and economical rAAV Fast Services to accelerate gene and cell therapy development efforts from discovery phase to commercialization.
Another Two-Plasmid AAV Gene Therapy Enters Clinical Trial: Gene Vector Biotechnology’s JWK001 Pioneers in Treating nAMD
On November 30, 2023, Gene Vector Biotechnology Co., Ltd. in Chengdu, China, received approval from the National Medical Products Administration's Center for Drug Evaluation (CDE) for the clinical trial of JWK001, a Class I gene therapy drug for treating neovascular...
Accelerating Gene Therapy Production: Combining next-generation AAV vectors and artificial intelligence (AI)
Recently, the France-based WIDGeT consortium emerged from a collaboration between Sanofi, WhiteLab Genomics, the TaRGeT Laboratory at Nantes University, and Institut Imagine. Scientists and companies in this consortium hope to speed up the development of gene...
First patient received dose level 2 of RGX-202, a potential one-time AAV Therapeutic for the treatment of Duchenne that includes an optimized transgene for a novel microdystrophin On track for pivotal dose determination and initiation of pivotal program in 2024...
Hodgkin lymphoma, nodular lymphocyte predominant (high-power view) Credit: Gabriel Caponetti, MD./Wikipedia/CC BY-SA 3.0The University of Pennsylvania plans to continue offering CAR-T therapy, a cancer treatment pioneered at Penn, after the Food and Drug...
AAV Packaging - NHP Grade
Off the Shelf AAV Products
We offer a wide catalogue of pre-made AAVs for a multitude of research needs.
AAV Capsid Engineering
Proven technology paving your path to effective therapies for cancer or genetic disorder