Gene Therapy

The focus of our research group is the development of therapeutic strategies for retinal pathologies, using advanced in vitro and animal models.

For this, we employ gene therapy strategies based on non-viral vectors for diseases such as diabetic retinopathy, retinopathy of prematurity, Lebers’ Congenital Amaurosis and Retinitis Pigmentosa.

For this purpose, our approach is four-fold:

Develop non-viral vectors based on natural and synthetic polymers such as chitosan, hyaluronic acid, and PDMAEMA.
Optimize of the delivery and expression of genes of interest, using more efficient plasmid-based expression systems and linkage of nuclear localization signals.
Contribute to the definition of the ethiology and identification of new therapeutic approaches for treating retinal diseases, with emphasis on RAS (Renin Angiotensin-System), PEDF and anti-angiogenic VEGF isoforms.
Use combinatorial approaches to efficiency target specific retinal cells.

Projects

2021-present: PTDC/CTM/REF/2679/2020 – SmartGlauco - Smart Drug Delivery Device for Glaucoma Treatment. Researcher (Principal Investigator at NMS). Foundation for Science and Technology (FCT), Portugal. 2021-2025.
The objective of this project is the development of controlled drug-release films for the post-surgical management of glaucoma.
2021-present: FCT Funding: PTDC/BTM-ORG/0500/2021: Principal Investigator.
The goal of this project was to explore the therapeutic potential of RBP3 in retinal gene therapy, in particular in monogenic diseases using in vitro and in vivo models.
2018-present: (Funding from FCT and other entities): Our long-term goal is the development of gene therapy-based therapies for diabetic retinopathy based on growth factor receptors and the RAS system.

Publications

D.B. Bitoque, G.A. Silva. Molecular biology tools for the study and therapy of PDE6beta mutations. Journal of Biotechnology, 284, pp 1-5. https://doi.org/10.1016/j.jbiotec.2018.07.030.
R.S Araújo, M.S. Silva, D.F. Santos, G.A. Silva. Dysregulation of trophic factors contributes to diabetic retinopathy in the Ins2Akita mouse. Experimental Eye Research. Vol 194. May 2020, 108027. https://doi.org/10.1016/j.exer.2020.108027.
R.S. Araújo, D.B. Bitoque, G.A. Silva. Dual-acting antiangiogenic gene therapy reduces inflammation and regresses neovascularization in diabetic mouse retina. Molecular Therapy. 2020; 22:329.339. doi: 10.1016/j.omtn.2020.08.036.
D.B. Bitoque*, J. Morais*, A.V. Oliveira*, S. Simão, T.M. Fortunato, S.M. Calado, R. Sequeira, A.M Rosa da Costa, G.A. Silva. Human-derived NLS enhance nonviral transfection. Bioscience Reports. 2021. 41(1). doi:10.1042/BSR20201026. *Equal contribution.
R.S. Araújo, D.B. Bitoque, G.A. Silva. Development of Strategies to Modulate Gene Expression of Angiogenesis-related Molecules in the Retina. Gene 791, 145724. https://doi.org/10.1016/j.gene.2021.145724.
A.M.L. Oliveira, M. Machado, G.A. Silva, D.B. Bitoque, J. Ferreira, L.A. Pinto, Q. Ferreira. Graphene Oxide Thin Films with Drug Delivery Function. Nanomaterials 2022, 12(7), 1149. doi: 10.3390/nano12071149.
D.B. Bitoque*, C. Fernandes*, A.M.L. Oliveira, G.A. Silva. Strategies to improve the targeting of retinal cells by gene therapy vectors . Frontiers in Drug Delivery. *Equally contributing authors. doi: 10.3389/fddev.2022.899260.
S. Talebin, B. Mendes, J. Conniot, D.B. Bitoque, G.A.Silva, J. Conde, G.G. Wallace. Biopolymeric coatings for local release of therapeutics from biomedical implants. Advanced Science. Impact factor: 17.52. https://doi.org/10.1002/advs.202207603.
D.B. Bitoque, S.M. Calado, A.M. Rosa da Costa, G.A. Silva. PDMAEMA gene vectors efficiently express PDE6β in a mouse model of retinitis pigmentosa. Biorxiv. https://www.biorxiv.org/content/10.1101/2023.05.04.538567v1.
F. Serdoura Alves; S. Duarte; A. Cabrita; C. Marques; A. Oliveira; M. Machado; G.A. Silva; L. Abegão Pinto; J. Tavares Ferreira; Q. Ferreira. Nanotechnology Devices for Glaucoma Surgical Treatment: A Systematic Review. Journal of Vision. (deposited in Preprints 2023, 2023091935. https://doi.org/10.20944/preprints202309.1935.v1

Prizes and Awards

2015: Travel Award for best podium communications, awarded to the following paper: S.M. Calado, L. Alves, G.A. Silva. Hyperglycemia and hypoxia induce overexpression of GLUT1 in models of diabetic retinopathy. EASD Annual Meeting 2015, Stockholm, September 2015.
2016: Janssen Innovation Award 2016: Honorable mention for the paper "Aliskeren as a new therapeutic approach for the treatment of diabetic retinopathy."
2018: Best Poster Award, awarded to the following paper: D.F. Santos, M. Pais, C.S. SANTOS, G. A. Silva. Can (poly)phenol metabolites ameliorate the outcome of diabetic retinopathy?. 2nd International Conference on Food Bioactives and Health, Portugal, 2018. Poster presentation.
2019: Poster presentation entitled: "Characterization and Modulation of the Renin-Angiotensin System: Towards a New Therapy for Diabetic Retinopathy," by Brigite Cabrita, D.F. SANTOS, G.A. Silva, selected as a finalist in the iMed 11.0(R) Innovation Contest.
2020: Best Oral Presentation Award for R. Araújo, G.A. Silva, "Dual Gene Therapy Approach for the Treatment of Diabetic Retinopathy." National Meeting of the Brazilian Society of Diabetology. 2020.
2020: Dr. Almeida Ruas Award, Best Clinical Project. G.A. Silva, "Analysis of Systematic Levels of Angiogenic and Antiangiogenic Factors in Diabetic Retinopathy." Brazilian Society of Diabetology. 2020.

Open Positions

PhD and Post Doc Opportunities @ Gabriela Silva's Lab

Grants

Know more

Research Grant (BI), for the conduct of R&D activities by a graduate with a Master degree enrolled in a course non-leading to an academic degree - Ref. ª SAI/2025/06

Grants

There is an open call for applications for a Research Grant (BI), for the conduct of R&D activities by a graduate with a Master degree enrolled in a course non-leading to an academic degree, under reference SAI/2025/06 in the scope of the NovaGo project, at the institution Faculdade de Ciências Médicas|NOVA Medical School (FCM|NMS) from Universidade NOVA de Lisboa (UNL), supported by income from the above mentioned project, financed by NovaGo Therapeutics AG.

Field of study: Biomedicine

Link for EURAXESS: Notice SAI/2025/06

Know more

Research Grant (BI), for the conduct of R&D activities by a graduate with a Master degree enrolled in a course non-leading to an academic degree - Ref. SF/2025/15

Grants

There is an open call for applications for a Research Grant (BI), for the conduct of R&D activities by a graduate with a Master degree enrolled in a course non-leading to an academic degree, under reference SF/2025/15 in the scope of the NovaGo project, at the institution Faculdade de Ciências Médicas|NOVA Medical School (FCM|NMS) from Universidade NOVA de Lisboa (UNL), supported by income from the above mentioned project, financed by NovaGo Therapeutics AG, under the following conditions:

Field of study: Biomedicine

Link for EURAXESS: Notice SF/2025/15

Know more