A Multiple-Site, Phase 1/2, Safety and Efficacy Trial of a Recombinant Adeno-associated Virus Vector Expressing CNGB3 in Patients With Congenital Achromatopsia Caused by Mutations in the CNGB3 Gene

This will be a non-randomized, open-label, Phase 1/2 study of the safety and efficacy of AGTC-401 administered to one eye by subretinal injection in individuals with achromatopsia caused by mutations in the CNGB3 gene. The primary study endpoint will be safety and the secondary study endpoint will be efficacy.

Start Date11 Apr 2016

Sponsor / Collaborator

Beacon Therapeutics (USA), Inc.

[+1]

100 Clinical Results associated with Raav2Tyf-Pr1.7-Hcngb3\xa0(Applied Genetic Technologies Corp.)

100 Translational Medicine associated with Raav2Tyf-Pr1.7-Hcngb3\xa0(Applied Genetic Technologies Corp.)

100 Patents (Medical) associated with Raav2Tyf-Pr1.7-Hcngb3\xa0(Applied Genetic Technologies Corp.)

Literatures (Medical) associated with Raav2Tyf-Pr1.7-Hcngb3\xa0(Applied Genetic Technologies Corp.)

01 Dec 2022·Molecular Therapy

Long-term safety of MRI-guided administration of AAV2-GDNF and gadoteridol in the putamen of individuals with Parkinson’s disease

Article

Author: Rocco, Matthew T ; Fiandaca, Massimo S ; Hallett, Mark ; Lungu, Codrin ; Scott, Gretchen C ; Bankiewicz, Krystof S ; Lonser, Russell R ; Aquino, Anthony ; Heiss, John D ; Akhter, Asad S ; Munjal, Vikas ; Ehrlich, Debra J

Direct putaminal infusion of adeno-associated virus vector (serotype 2) (AAV2) containing the human glial cell line-derived neurotrophic factor (GDNF) transgene was studied in a phase I clinical trial of participants with advanced Parkinson's disease (PD). Convection-enhanced delivery of AAV2-GDNF with a surrogate imaging tracer (gadoteridol) was used to track infusate distribution during real-time intraoperative magnetic resonance imaging (iMRI). Pre-, intra-, and serial postoperative (up to 5 years after infusion) MRI were analyzed in 13 participants with PD treated with bilateral putaminal co-infusions (52 infusions in total) of AAV2-GDNF and gadoteridol (infusion volume, 450 mL per putamen). Real-time iMRI confirmed infusion cannula placement, anatomic quantification of volumetric perfusion within the putamen, and direct visualization of off-target leakage or cannula reflux (which permitted corresponding infusion rate/cannula adjustments). Serial post-treatment MRI assessment (n = 13) demonstrated no evidence of cerebral parenchyma toxicity in the corresponding regions of AAV2-GDNF and gadoteridol co-infusion or surrounding regions over long-term follow-up. Direct confirmation of key intraoperative safety and efficacy parameters underscores the safety and tissue targeting value of real-time imaging with co-infused gadoteridol and putative therapeutic agents (i.e., AAV2-GDNF). This delivery-imaging platform enhances safety, permits delivery personalization, improves therapeutic distribution, and facilitates assessment of efficacy and dosing effect.

18 Oct 2020·Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences

[Expression pattern of different serotypes of adeno-associated viral vectors in mouse retina].

Article

Author: Hu Shuang ; Yang Li-ping

OBJECTIVETo investigate the expression efficiency of exogenous gene mediated by different serotypes of adeno-associated virus (AAV) vectors in retina, and to compare the expression efficiency of AAV vector and two kinds of promoters commonly used in ophthalmology after transfection into mouse retina, so as to provide the basis for selecting appropriate AAV vector and promoter for gene therapy of retinitis pigmentosa.METHODSAAV2/2, AAV2/5, AAV2/8 and AAV2/9 were prepared. The C57BL/6J mice were injected subretinally with 1 μL purified AAV vectors (1.00×10¹³ mg/L). Then the mice were killed 2 or 4 weeks after treatment, and the eyes were enucleated for frozen section. The expression of green fluorescent protein (GFP) was observed under the confocal microscope. Two kinds of promoters, CMV and CAG, were selectd, and the expression of AAV2/8-GFP-CMV and AAV2/8-GFP-CAG was observed under confocal microscope.RESULTSNo bacterial infection or immune response were seen in the injected mice. 2 weeks after injection, the GFP green fluorescence of AAV2/8 and AAV2/9 in the mouse retina was obvious, which indicated that the GFP green fluorescence of AAV2/8 and AAV2/9 was high after transfection into the mouse retina. In these two serotypes, GFP green fluorescence of AAV2/8 was mainly concentrated in photoreceptor cells while AAV2/8 was expressed in the whole retina, indicating that AAV2/8 was more specific to photoreceptors. Further experiments on AAV2/8 showed that the GFP green fluorescence of the mouse retina was obvious 4 weeks after injection, indicating that the exogenous gene mediated by AAV2/8 could be stably expressed in vivo. For CMV and CAG promoters, CMV promoter was expressed stronger in retinal pigment epithelium (RPE)cells, while CAG promoter was stronger in photorecepters. In photorecepters, CAG promoter was expressed almost the same as CMV promoter, while CMV promoter was stronger in RPE cells.CONCLUSIONAAV vectors could express transgene robustly in retinal cells; Among several AAV serotypes, AAV2/2 and AAV2/5 showed weaker GFP fluorescence than AAV2/8 and AAV2/9. AAV2/9 showed expression in each layer of the retina including ganglion cells. AAV2/8 was more specific for photoreceptor; CAG promoters had higher specificity for photoreceptors than CMV promoters.

01 Apr 2020·Human Gene TherapyQ2 · MEDICINE

Different Serotypes of Adeno-Associated Virus Vector- and Lentivirus-Mediated Tropism in Choroid Plexus by Intracerebroventricular Delivery

Q2 · MEDICINE

Article

Author: Wang, Haiyang ; He, Yong ; Xie, Peng ; Wu, Zhonghao ; Wang, Yue ; Lan, Tianlan ; Cheng, Ke ; Chen, Xi ; Tian, Yu

Regulation of gene expression by viral vectors is an effective method for researchers to explore the function of gene products in a target tissue. The choroid plexus (CP) is an important target for gene therapy of neuropsychiatric diseases such as Alzheimer's disease and major depressive disorder. However, viral tropism in CP has not been well studied as a result of limited viral vector applications. To identify CP-specific viral vectors, we intracerebroventricularly administered six different serotypes of adeno-associated virus (AAV) vectors (AAV2/1, AAV2/5, AAV2/8, AAV2/9, AAV2-BR1, and AAV2-PHP.eB) and lentivirus in adult mice. Tropism in CP was compared among these viruses. We found that AAV2/5 and AAV2/8 displayed remarkable infections in CP, while AAV2/1 infected both ependymal cells and cells in the CP. Except for the low infection intensity of AAV2/9 and lentivirus in the CP, no infection intensity was found for CP tissues injected with AAV2-BR1 or AAV2-PHP.eB. Green fluorescence protein expression in the CP after AAV2/5 infection was confirmed by Western blotting. AAV2/5-mediated tropism in epithelial cells of the CP was verified by immunostaining with transthyretin. In this study, we identified for the first time that serotype-specific AAVs 5 and 8 may be robust research tools for intracerebroventricular gene delivery.

100 Deals associated with Raav2Tyf-Pr1.7-Hcngb3\xa0(Applied Genetic Technologies Corp.)

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Color Vision Defects	Phase 2	US	Beacon Therapeutics (USA), Inc.	01 Feb 2016
Color Vision Defects	Phase 2	IL	Beacon Therapeutics (USA), Inc.	01 Feb 2016

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


AAV2/8 (ASGCT2012)	Not Applicable	neutralizing antibodies (NAbs)	8	AAV2/8	dobrbqezyd(uogwlqkjqg) = aehdzulfub fyvztjgsye (xyalwejhxp, 108)	Positive	01 May 2012
ASGCT2010	Not Applicable	Ornithine Carbamoyltransferase Deficiency Disease	-	AAV2/8 Based Vector	xvvxemeorf(dxwmyabhfy) = ymybrsgvyl becjuwryrp (jycmrmsery )	-	01 May 2010
ASGCT2007	Not Applicable	HIV Infections	-	AAV 2/8	hizgikevpl(hdfvjkrsmr) = ddkdlgkxrx mbcplkiose (jxkllainpb )	-	01 May 2007

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