Neurotrophin gene augmentation by electrotransfer to improve cochlear implant hearing outcomes

Pinyon, Jeremy L.; Jonquières, Georg von; Crawford, Edward N.; Duxbury, Mayryl; Abed, Amr Al; Lovell, Nigel H.; Klugmann, Matthias; Wise, Andrew K.; Fallon, James B; Shepherd, Robert K.; Birman, Catherine S.; Lai, Wai Kong; McAlpine, David; McMahon, Catherine M.; Carter, Paul; Enke, Ya Lang; Patrick, J.; Schilder, Anne G. M.; Marie, Corinne; Scherman, Daniel; Housley, Gary D.

doi:10.1016/j.heares.2019.06.002

Cited by 25 publications

(18 citation statements)

References 65 publications

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“…Mice have well characterized genomes, with genetic, biological, and behavioral characteristics similar to humans, and their genomes can be easily manipulated which is a boon for studies of inherited diseases. Guinea pigs have also been used for evaluation of auditory dysfunction as they are susceptible to noise induced hearing loss, making them a commonly used model for optimizing gene delivery approaches and to assess the efficacy of gene-based treatments not targeted to a specific disease gene (for example delivery of growth factors for general neuroprotection) (Chen et al, 2018;Pinyon et al, 2019;Lafond et al, 2020). Final preclinical studies for both safety and efficacy use larger animal models, including pigs, dogs, and non-human primates, as these animals may better mimic the anatomy or immune system of human structures or because they offer further evidence of efficacy, for example in the RPE65 dog model (Kelley et al, 2018;Maddalena et al, 2018;Ding et al, 2019;Gyorgy et al, 2019;Gardiner et al, 2020;Ivanchenko et al, 2020).…”

Section: The Use Of Animal Models To Study Retinal and Cochlear Inherited Diseasesmentioning

confidence: 99%

Gene Therapy to the Retina and the Cochlea

et al. 2021

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Vision and hearing disorders comprise the most common sensory disorders found in people. Many forms of vision and hearing loss are inherited and current treatments only provide patients with temporary or partial relief. As a result, developing genetic therapies for any of the several hundred known causative genes underlying inherited retinal and cochlear disorders has been of great interest. Recent exciting advances in gene therapy have shown promise for the clinical treatment of inherited retinal diseases, and while clinical gene therapies for cochlear disease are not yet available, research in the last several years has resulted in significant advancement in preclinical development for gene delivery to the cochlea. Furthermore, the development of somatic targeted genome editing using CRISPR/Cas9 has brought new possibilities for the treatment of dominant or gain-of-function disease. Here we discuss the current state of gene therapy for inherited diseases of the retina and cochlea with an eye toward areas that still need additional development.

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Section: The Use Of Animal Models To Study Retinal and Cochlear Inherited Diseasesmentioning

confidence: 99%

Gene Therapy to the Retina and the Cochlea

et al. 2021

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“…Ex-vivo gene addition and gene editing are readily achievable employing non – viral approaches including gene – electrotransfer. A notable advantage of gene editing is the preservation of normal copy numbers and gene regulation ( Pinyon et al, 2019 ; Wagenblast et al, 2019 ). A recent study has modified induced neural progenitor cells (NPCs) and induced oligodendroglial progenitor cells (OPCs) from Canavan disease (CD) patients to express human aspartoacylase ( ASPA ) via lentivirus mediated gene addition and TALEN mediated gene editing.…”

Section: Ex Vivo Gene Therapymentioning

confidence: 99%

Emerging Concepts in Vector Development for Glial Gene Therapy: Implications for Leukodystrophies

Jonquières

Rae

Housley

2021

Front. Cell. Neurosci.

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Central Nervous System (CNS) homeostasis and function rely on intercellular synchronization of metabolic pathways. Developmental and neurochemical imbalances arising from mutations are frequently associated with devastating and often intractable neurological dysfunction. In the absence of pharmacological treatment options, but with knowledge of the genetic cause underlying the pathophysiology, gene therapy holds promise for disease control. Consideration of leukodystrophies provide a case in point; we review cell type – specific expression pattern of the disease – causing genes and reflect on genetic and cellular treatment approaches including ex vivo hematopoietic stem cell gene therapies and in vivo approaches using adeno-associated virus (AAV) vectors. We link recent advances in vectorology to glial targeting directed towards gene therapies for specific leukodystrophies and related developmental or neurometabolic disorders affecting the CNS white matter and frame strategies for therapy development in future.

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“…For DNA vaccination or gene therapy applications efficient delivery of plasmid DNA [1] or short RNA molecules [2] is crucial. Gene therapy is based on insertion of healthy genes or alteration or removal of defective genes responsible for disease development [3].…”

Section: Introductionmentioning

confidence: 99%

“…Electroporation is already successfully applied in different biomedical applications, including: electrofusion [13,14]; electrochemotherapy [15,16]; irreversible tissue ablation [17]; DNA vaccination [18,19] and gene electrotransfer [20][21][22]. Today gene electrotransfer is widely used to introduce DNA into different cells [23,24] and tissues [1,25,26] due to its efficiency, safety and easy application. It is also relevant in a variety of clinical settings including cancer therapy, modulation of pathogenic immune responses, delivery of therapeutic proteins and drugs [27,28].…”

Section: Introductionmentioning

confidence: 99%

Analysis of DNA mobility and gene electrotransfer in 3D in vitro collagen gel model

Meglič

Pavlin

2020

Preprint

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Background: Gene electrotransfer is an established method that enables transfer of DNA into cells with electric pulses. Several studies analyzed different parameters; however the question of the mechanisms involved in gene electrotransfer remains open. One of main obstacles toward efficient gene electrotransfer in vivo is relatively poor DNA mobility in tissues.Objective and method: In order to analyze the effect of impaired mobility on gene electrotransfer efficiency, we applied electric pulses with different durations on plated cells, cells grown on collagen layer and cells embedded in collagen gel (3D model) and compared gene electrotransfer efficiency and viability of cells.Results: We obtained the highest transfection of plated cells, while transfection efficiency of embedded cells in 3D model was lowest and similar as in in vivo. To further analyze poor DNA mobility in 3D model, we applied DNA in top of or injected it into 3D model and showed that former way increases gene electrotransfer efficiency as was shown in in vivo studies.Conclusion: We reported empirically and theoretically evidence that DNA has impaired mobility and diffusion in collagen environment. In addition our method provides resembling in vivo situation, where gene electrotransfer mechanisms can be studied.

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Neurotrophin gene augmentation by electrotransfer to improve cochlear implant hearing outcomes

Cited by 25 publications

References 65 publications

Gene Therapy to the Retina and the Cochlea

Gene Therapy to the Retina and the Cochlea

Emerging Concepts in Vector Development for Glial Gene Therapy: Implications for Leukodystrophies

Analysis of DNA mobility and gene electrotransfer in 3D in vitro collagen gel model

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