Macrophage Inhibitor Clodronate Enhances Liver Transduction of Lentiviral but Not Adeno-Associated Viral Vectors or mRNA Lipid Nanoparticles in Neonatal and Juvenile Mice DOI Creative Commons

Loukia Touramanidou,

Sonam Gurung, Andrei Claudiu Cozmescu

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(23), P. 1979 - 1979

Published: Nov. 29, 2024

Recently approved adeno-associated viral (AAV) vectors for liver monogenic diseases haemophilia A and B are exemplifying the success of liver-directed gene therapy. In parallel, additional therapy strategies rapidly emerging to overcome some inherent AAV limitations, such as non-persistence episomal transgene in growing immune response. Viral integrating vivo lentiviral non-viral lipid nanoparticles encapsulating mRNA (LNP-mRNA) being developed, currently at preclinical clinical stages, respectively. Macrophages first effector cells innate response triggered by vectors. Macrophage uptake activation following administration LNP have been reported. this study, we assessed biodistribution AAV, lentiviral, LNP-mRNA depletion tissue macrophages clodronate pre-treatment neonatal juvenile mice. Both adult clodronate-treated mice showed a significant increase lentiviral-transduced hepatocytes. contrast, did not modify hepatocyte transduction mediated hepatotropic AAV8 but reduced transfection animals. These results highlight importance age-specific responses will translational applications programs.

Language: Английский

Long-term experience with gene augmentation therapy in patients with inherited retinal disease associated with biallelic mutations in RPE65 DOI Creative Commons

Birgit Lorenz

Medizinische Genetik, Journal Year: 2025, Volume and Issue: 37(1), P. 47 - 56

Published: Feb. 6, 2025

Language: Английский

Citations

1
Gene Therapy-Associated Uveitis (GTAU): Understanding and mitigating the adverse immune response in retinal gene therapy DOI Creative Commons

Ryan Purdy,

Molly John,

AE Bray

et al.

Progress in Retinal and Eye Research, Journal Year: 2025, Volume and Issue: unknown, P. 101354 - 101354

Published: March 1, 2025

Retinal gene therapy using adeno-associated viral (AAV) vectors has been a groundbreaking step-change in the treatment of inherited retinal diseases (IRDs) and could also be used to treat more common such as age-related macular degeneration diabetic retinopathy. The delivery expression therapeutic transgenes eye is limited by innate adaptive immune responses against components vector product, which termed therapy-associated uveitis (GTAU). This clinically important intraocular inflammation lead irreversible loss cells, deterioration visual function reduced durability effect associated with costly one-off treatment. For achieve an improved efficacy safety profile for treating additional IRDs diseases, risk GTAU must minimised. We have collated insights from pre-clinical research, clinical trials, real-world implementation AAV-mediated help understand factors GTAU. draw attention emerging framework, includes patient demographics, construct, dose, route administration, choice immunosuppression regime. Importantly, we consider efforts date potential future strategies mitigate adverse response across each these domains. advocate targeted immunomodulatory approaches prevention based on better understanding underlying response.

Language: Английский

Citations

1
Immune responses to central nervous system directed adeno-associated virus gene therapy: Does direct CNS delivery make a difference? DOI Creative Commons

Ashley L. Harkins,

Prajakta P Ambegaokar,

Allison M. Keeler

et al.

Neurotherapeutics, Journal Year: 2024, Volume and Issue: 21(4), P. e00435 - e00435

Published: July 1, 2024

Language: Английский

Citations

6
Nanovaccine enables complement system inhibition and high-dose AAV re-administration DOI
Zhenrui Liao, Yu Jiang, Fei Liang

et al.

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: unknown, P. 160810 - 160810

Published: Feb. 1, 2025

Citations

0
Extracellular vesicles for the delivery of gene therapy DOI
Emilio Di Ianni,

Wataru Obuchi,

Koen Breyne

et al.

Nature Reviews Bioengineering, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Language: Английский

Citations

0
Klotho alleviates sepsis-associated myocardial inflammation and apoptosis DOI
Zhongcheng Wei, Juan Liu,

Hailang Liu

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177653 - 177653

Published: April 1, 2025

Language: Английский

Citations

0
Recent Advances in Designing Adeno-Associated Virus-Based Vaccines Against Viral Infections DOI Creative Commons
Njabulo Mnyandu,

Ridhwaanah Jacobs,

Patrick Arbuthnot

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(11), P. 1360 - 1360

Published: Oct. 24, 2024

Over 80% of the world's deadliest pandemics are caused by viral infections, and vaccination remains most effective way to prevent these infections from spreading. Since discovery first vaccine over two centuries ago, several design technologies have been developed. Next-generation vaccines, based on mRNA vector technologies, recently emerged as alternatives traditional vaccines. Adenoviral vector-based vaccines against coronavirus disease 2019 demonstrated a more sustained antibody response compared However, this has not without complications, with few cases severe adverse events identified in vaccinated individuals, underlying mechanism is subject intense investigation. Adeno-associated vectors induce weaker cellular immune adenoviral vectors, it mainly for reason that there diminished interest exploring them platform until recently. This review will discuss recent developments potential adeno-associated anti-viral

Language: Английский

Citations

1
Redundancy in Innate Immune Pathways That Promote CD8+ T-Cell Responses in AAV1 Muscle Gene Transfer DOI Creative Commons
Ning Li, Sandeep Kumar, Di Cao

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(10), P. 1507 - 1507

Published: Sept. 24, 2024

While adeno-associated viral (AAV) vectors are successfully used in a variety of vivo gene therapy applications, they continue to be hampered by the immune system. Here, we sought identify innate and cytokine signaling pathways that promote CD8

Language: Английский

Citations

0
Gene Therapy in the Light of Lifestyle Diseases: Budesonide, Acetaminophen and Simvastatin Modulates rAAV Transduction Efficiency DOI Creative Commons
Żaneta Słyk,

Natalia Stachowiak,

Maciej Małecki

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(9), P. 1213 - 1213

Published: Sept. 14, 2024

Recombinant AAV (rAAV) vectors are increasingly favored for gene therapy due to their useful features of vectorology, such as transfection dividing and nondividing cells, the presence tissue-specific serotypes, biosafety considerations. This study investigates impact commonly used therapeutic drugs—acetaminophen, budesonide, simvastatin—on rAAV transduction efficiency in HEK-293 cells. Cells were transduced with an mosaic vector under control a cytomegalovirus (CMV) promoter encoding green fluorescent protein (GFP). Transduction was assessed by qPCR microscopy. Analysis functional interactions between genes potentially involved drug-exposed cells also performed. showed clear effect drugs on transmission. Notably, acetaminophen enhanced 9-fold, while budesonide simvastatin 2-fold 3-fold increases, respectively. The analysis illustrates possible involvement related cell membranes potentiation induced investigation. Attention should be paid S100A8, which is common drug-modified showing anti-inflammatory effects (budesonide simvastatin), demonstrating interaction receptor (HGFR). underscores significance assessing pharmacokinetics/pharmacodynamics (PKs/PDs) drug–gene optimizing protocols.

Language: Английский

Citations

0
Macrophage Inhibitor Clodronate Enhances Liver Transduction of Lentiviral but Not Adeno-Associated Viral Vectors or mRNA Lipid Nanoparticles in Neonatal and Juvenile Mice DOI Creative Commons

Loukia Touramanidou,

Sonam Gurung, Andrei Claudiu Cozmescu

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(23), P. 1979 - 1979

Published: Nov. 29, 2024

Recently approved adeno-associated viral (AAV) vectors for liver monogenic diseases haemophilia A and B are exemplifying the success of liver-directed gene therapy. In parallel, additional therapy strategies rapidly emerging to overcome some inherent AAV limitations, such as non-persistence episomal transgene in growing immune response. Viral integrating vivo lentiviral non-viral lipid nanoparticles encapsulating mRNA (LNP-mRNA) being developed, currently at preclinical clinical stages, respectively. Macrophages first effector cells innate response triggered by vectors. Macrophage uptake activation following administration LNP have been reported. this study, we assessed biodistribution AAV, lentiviral, LNP-mRNA depletion tissue macrophages clodronate pre-treatment neonatal juvenile mice. Both adult clodronate-treated mice showed a significant increase lentiviral-transduced hepatocytes. contrast, did not modify hepatocyte transduction mediated hepatotropic AAV8 but reduced transfection animals. These results highlight importance age-specific responses will translational applications programs.

Language: Английский

Citations

0