scholarly journals The Degeneration and Apoptosis Patterns of Cone Photoreceptors in rd11 Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Hua Zhang ◽  
Xia Li ◽  
Xufeng Dai ◽  
Juanjuan Han ◽  
Yangyang Zhang ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Animal Model ◽  
Direct Relationship ◽  
Distribution Patterns ◽  
Photoreceptor Degeneration ◽  
Cone Photoreceptors ◽  
Cone Function ◽  
Key Genes ◽  
Apoptotic Signal

The retinal degeneration 11 (rd11) mouse is a new animal model with rapid photoreceptor degeneration. The long-term efficacy of gene therapy has a direct relationship with the onset of photoreceptor degeneration or apoptosis, whereas the degeneration or apoptosis patterns of photoreceptors are still unclear in rd11 mice. The distribution patterns of cone function-related L- and S-opsin were examined by immunofluorescence staining, and the apoptosis was performed by TUNEL assay in rd11 mice. The expression pattern of L-opsin or S-opsin in rd11 retina at postnatal day (P) 14 was similar to the pattern observed in wildtype retina. With increasing age, the expression of L-opsin and S-opsin, especially S-opsin, decreased significantly in rd11 mice. The degeneration of L-opsin began around the optic nerve and expanded to the periphery of the retina, from the ventral/nasal to dorsal/temporal retina, whereas the expression of S-opsin gradually decreased from the dorsal/temporal to ventral/nasal retina. Apoptotic signal appeared at P14 and was strongest at P28 of rd11 mice. The key genes associated with apoptosis confirmed those changes. These indicated that the degeneration and apoptosis of cone photoreceptors began at P14 of rd11 mice, which was a key point for gene therapy.

scholarly journals Long-term lymphoid progenitors independently sustain naïve T and NK cell production in humans

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Natalia Izotova ◽  
Christine Rivat ◽  
Cristina Baricordi ◽  
Elena Blanco ◽  
Danilo Pellin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Nk Cell ◽  
Integration Site ◽  
Hematopoietic Stem ◽  
Cell Production ◽  
Lymphoid Progenitors ◽  
Clinical Gene Therapy ◽  
Cancer Immunotherapies

AbstractOur mathematical model of integration site data in clinical gene therapy supported the existence of long-term lymphoid progenitors capable of surviving independently from hematopoietic stem cells. To date, no experimental setting has been available to validate this prediction. We here report evidence of a population of lymphoid progenitors capable of independently maintaining T and NK cell production for 15 years in humans. The gene therapy patients of this study lack vector-positive myeloid/B cells indicating absence of engineered stem cells but retain gene marking in both T and NK. Decades after treatment, we can still detect and analyse transduced naïve T cells whose production is likely maintained by a population of long-term lymphoid progenitors. By tracking insertional clonal markers overtime, we suggest that these progenitors can support both T and NK cell production. Identification of these long-term lymphoid progenitors could be utilised for the development of next generation gene- and cancer-immunotherapies.

scholarly journals Gene Therapy in Hemophilia: Recent Advances

2021 ◽  
Vol 22 (14) ◽  
pp. 7647
Author(s):  
E. Carlos Rodríguez-Merchán ◽  
Juan Andres De Pablo-Moreno ◽  
Antonio Liras
Keyword(s):  
Gene Therapy ◽  
Adverse Events ◽  
Factor Viii ◽  
Coagulation Factor ◽  
Cost Savings ◽  
Factor Ix ◽  
Clotting Factors ◽  
Advanced Therapies ◽  
Potential Benefits

Hemophilia is a monogenic mutational disease affecting coagulation factor VIII or factor IX genes. The palliative treatment of choice is based on the use of safe and effective recombinant clotting factors. Advanced therapies will be curative, ensuring stable and durable concentrations of the defective circulating factor. Results have so far been encouraging in terms of levels and times of expression using mainly adeno-associated vectors. However, these therapies are associated with immunogenicity and hepatotoxicity. Optimizing the vector serotypes and the transgene (variants) will boost clotting efficacy, thus increasing the viability of these protocols. It is essential that both physicians and patients be informed about the potential benefits and risks of the new therapies, and a register of gene therapy patients be kept with information of the efficacy and long-term adverse events associated with the treatments administered. In the context of hemophilia, gene therapy may result in (particularly indirect) cost savings and in a more equitable allocation of treatments. In the case of hemophilia A, further research is needed into how to effectively package the large factor VIII gene into the vector; and in the case of hemophilia B, the priority should be to optimize both the vector serotype, reducing its immunogenicity and hepatotoxicity, and the transgene, boosting its clotting efficacy so as to minimize the amount of vector administered and decrease the incidence of adverse events without compromising the efficacy of the protein expressed.

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