The Role of Attractiveness in Gendered Sexual Response Patterns.

Previously documented sexual response patterns of gender-specificity among gynephilic men and gender-nonspecificity among gynephilic women could be explained by women responding more strongly to non-gendered aspects of sexual stimuli. Cues of attractiveness are known determinants of sexual decision-making, yet have not been directly tested as determinants of sexual response. The current study investigated the role of attractiveness cues in explaining gender-based patterns of sexual response.

AAV Gene Augmentation of Truncated Complement Factor H Differentially Rescues Ocular Complement Dysregulation in a Mouse Model.

Purpose: Complement dysregulation in the eye has been implicated in the pathogenesis of age-related macular degeneration (AMD), and genetic variants of complement factor H (CFH) are strongly associated with AMD risk. We therefore aimed to untangle the role of CFH and its splice variant, factor H-like 1 (FHL-1), in ocular complement regulation derived from local versus circulating sources. We assessed the therapeutic efficacy of adeno-associated viruses (AAVs) expressing human FHL-1 and a truncated version of CFH (tCFH), which retains the functional N- and C-terminal ends of the CFH protein, in restoring the alternative complement pathway in Cfh-/- mouse eyes and plasma.

Towards Advanced iPSC-based Drug Development for Neurodegenerative Disease.

Neurodegenerative diseases (NDDs) are a heterogeneous group of diseases that are characterized by the progressive loss of neurons leading to motor, sensory, and/or cognitive defects. Currently, NDDs are not curable and treatment focuses on alleviating symptoms and halting disease progression. Phenotypic heterogeneity between individual NDD patients, lack of robust biomarkers, the limited translational potential of experimental models, and other factors have hampered drug development for the treatment of NDDs.

Dose Range Finding Studies with Two Transgenes in a Canine Model of X-Linked Retinitis Pigmentosa Treated with Subretinal Gene Therapy.

Recombinant adeno-associated viral (rAAV) vector-mediated gene therapy is being developed to treat X-linked retinitis pigmentosa (XLRP) in patients with mutations in the retinitis pigmentosa GTPase regulator () gene. In preparation for a clinical gene therapy trial, we conducted dose range finding (DRF) studies with an AAV2 capsid with three surface tyrosine residues changed to phenylalanine (AAV2tYF) vector administered by subretinal injection in a naturally occurring -mutant canine model (XLPRA2) to compare two different human () transgenes and to establish a reasonable starting dose for a clinical trial. Different dose levels of two candidate vectors (0.

Toxicity and Efficacy Evaluation of an Adeno-Associated Virus Vector Expressing Codon-Optimized Delivered by Subretinal Injection in a Canine Model of X-linked Retinitis Pigmentosa.

Applied Genetic Technologies Corporation (AGTC) is developing a recombinant adeno-associated virus (rAAV) vector AGTC-501, also designated rAAV2tYF-GRK1-, to treat X-linked retinitis pigmentosa (XLRP) in patients with mutations in the retinitis pigmentosa GTPase regulator () gene. The vector contains a codon-optimized human RPGR cDNA () driven by a photoreceptor-specific promoter (G protein-coupled receptor kinase 1 [GRK1]), and is packaged in an AAV2 capsid variant with three surface tyrosine residues changed to phenylalanine (AAV2tYF). We conducted a toxicity and efficacy study of this vector administered by subretinal injection in the naturally occurring mutant (X-linked progressive retinal atrophy 2 [XLPRA2]) dog model.