Liver lobe-specific hydrodynamic gene delivery to baboons: A preclinical trial for hemophilia gene therapy

Kamimura, Kenya; Kanefuji, Tsutomu; Suda, Takafumi; Yokoo, Takeshi; Zhang, Guisheng; Aoyagi, Yoshinobu; Liu, Dexi

doi:10.1016/j.omtn.2023.05.018

Cited by 2 publications

(2 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This technique is largely applied in small rodents to compare liver-specific promoters in hepatocytes, but still awaits further developments for its translation in larger animals and humans. In dogs or non-human primates, the current procedure involves a liver lobe-specific, computer-controlled and image-guided plasmid hydrodynamic gene delivery [ 19 , 20 ].…”

Section: Chemical and Physical Delivery Techniquesmentioning

confidence: 99%

Antibiotic-Free Gene Vectors: A 25-Year Journey to Clinical Trials

Marie,

Scherman

2024

Genes

View full text Add to dashboard Cite

Until very recently, the major use, for gene therapy, specifically of linear or circular DNA, such as plasmids, was as ancillary products for viral vectors’ production or as a genetic template for mRNA production. Thanks to targeted and more efficient physical or chemical delivery techniques and to the refinement of their structure, non-viral plasmid DNA are now under intensive consideration as pharmaceutical drugs. Plasmids traditionally carry an antibiotic resistance gene for providing the selection pressure necessary for maintenance in a bacterial host. Nearly a dozen different antibiotic-free gene vectors have now been developed and are currently assessed in preclinical assays and phase I/II clinical trials. Their reduced size leads to increased transfection efficiency and prolonged transgene expression. In addition, associating non-viral gene vectors and DNA transposons, which mediate transgene integration into the host genome, circumvents plasmid dilution in dividing eukaryotic cells which generate a loss of the therapeutic gene. Combining these novel molecular tools allowed a significantly higher yield of genetically engineered T and Natural Killer cells for adoptive immunotherapies due to a reduced cytotoxicity and increased transposition rate. This review describes the main progresses accomplished for safer, more efficient and cost-effective gene and cell therapies using non-viral approaches and antibiotic-free gene vectors.

show abstract

Section: Chemical and Physical Delivery Techniquesmentioning

confidence: 99%

Antibiotic-Free Gene Vectors: A 25-Year Journey to Clinical Trials

Marie,

Scherman

2024

Genes

View full text Add to dashboard Cite

show abstract

“…The porcine model permitted evaluating the potential of this strategy to efficiently transfer a naked entire gene to the liver with enough bioavailability to be decoded and express high levels of the protein of interest. Recently, Kamimura et al [18] reported efficient gene transfer in the baboon liver by lobe-directed hydrodynamic injection employing IX coagulation factor. Aiming to determine whether this would occur in human beings, we developed a procedure to transfer a gene using the hydrodynamic procedure in watertight human liver segments derived from surgical resection in patients with cancer [19].…”

Section: Introductionmentioning

confidence: 99%

Safe Procedure for Efficient Hydrodynamic Gene Transfer to Isolated Porcine Liver in Transplantation

Sendra,

Navasquillo,

Montalvá

et al. 2024

IJMS

View full text Add to dashboard Cite

Although calcineurin inhibitors are very effective as immunosuppressants in organ transplantation, complete graft acceptance remains as a challenge. Transfer of genes with immunosuppressant functions could contribute to improving the clinical evolution of transplantation. In this sense, hydrodynamic injection has proven very efficacious for liver gene transfer. In the present work, the hIL-10 gene was hydrofected ‘ex vivo’ to pig livers during the bench surgery stage, to circumvent the cardiovascular limitations of the procedure, in a model of porcine orthotopic transplantation with a 10-day follow-up. We used IL-10 because human and porcine proteins can be differentially quantified and for its immunomodulatory pleiotropic functions. Safety (biochemical parameters and histology), expression efficacy (RNA transcription and blood protein expression), and acute inflammatory response (cytokines panel) of the procedure were evaluated. The procedure proved safe as no change in biochemical parameters was observed in treated animals, and human IL-10 was efficaciously expressed, with stationary plasma protein levels over 20 pg/mL during the follow-up. Most studied cytokines showed increments (interferon-α, IFN-α; interleukin-1β, IL-1β; tumor necrosis factor α, TNFα; interleukin-6, IL-6; interleukin-8, IL-8; interleukin-4, IL-4; and transforming growth factor-β, TGF-β) in treated animals, without deleterious effects on tissue. Collectively, the results support the potential clinical interest in this gene therapy model that would require further longer-term dose–response studies to be confirmed.

show abstract

Liver lobe-specific hydrodynamic gene delivery to baboons: A preclinical trial for hemophilia gene therapy

Cited by 2 publications

References 51 publications

Antibiotic-Free Gene Vectors: A 25-Year Journey to Clinical Trials

Antibiotic-Free Gene Vectors: A 25-Year Journey to Clinical Trials

Safe Procedure for Efficient Hydrodynamic Gene Transfer to Isolated Porcine Liver in Transplantation

Contact Info

Product

Resources

About