ITQB: CBL - PhD Theses
URI permanente para esta coleção:
Navegar
Entradas recentes
- Next generation of dual-AAV gene therapy systems: enhancing large transgene deliveryPublication . Ferreira, Mariana Massapina Valentim; Coroadinha, Ana Sofia"Gene therapy consists of treating a disease by transferring genetic material into the patient’s cells. Successful clinical trials have led to significant advancements in the treatment of previously untreatable diseases. Among the diverse viral vectors employed in gene therapy, adeno-associated virus (AAV) vectors are one of the gene delivery vehicles of choice, with a high representation in clinical trials and commercialised products. This is mainly because of AAV vectors’ safety profile, extensive cellular tropism, and capacity for sustained transgene expression.(...)"
- Advancing Biotherapeutic Manufacturing Through New Purification StrategiesPublication . Fernandes, Rita Patrício; Peixoto, Cristina; Mota, José Paulo"The bioprocessing of enveloped viral vectors and extracellular vesicles (EVs) has made significant advances in recent years, driven by their growing applications in gene therapy, vaccine development, and regenerative medicine. These biological entities, which include viral vectors such as lentiviruses, retroviruses, and oncolytic viruses, as well as therapeutic EVs, are essential for delivering genetic material and modulating intercellular communication. Their increasing relevance is reflected in the expanding number of clinical trials and therapeutic products leveraging these platforms. For instance, lentiviral vectors (LVs) have become critical tools in gene therapies targeting monogenic disorders and cell-based therapies, while extracellular vesicles are being explored for their potential in drug delivery and immune modulation. (...)"
- Biological and Engineering Approaches to Advance Bioprocesses for hiPSC-based ProductsPublication . Vicente, Pedro Miguel Gomes Gião; Serra, Margarida; Alves, Paula"Human pluripotent stem cells (hPSC), including induced pluripotent stem cells (hiPSC), have the unique ability to proliferate and differentiate into any cell type from the three primary germ layers. These properties have made hiPSC and derivatives attractive candidates for cell therapy, in vitro disease modelling, and as drug discovery platforms. To meet the global demand for PSC-derived cell therapies large number of cells are required. Therefore, the implementation of technologies that allow the systematic production of cells in a robust and cost-effective manner is essential. In addition, challenges such as process variability, differentiation efficiency, scalability and automation for process standardization must be addressed. Bioreactors-based systems that are designed to precisely control/regulate the cellular microenvironment offer a possible solution to overcome these challenges.(...)"
- Accelerating Lentivirus Manufacturing: An engineering-driven approachPublication . Costa Moreira, Ana Sofia; Peixoto, CristinaThe journey of Advanced Therapy Medicinal Products (ATMPs) has come a long way in the last few decades, as is reflected in the increasing number of clinical trials conducted every year. Particularly, in the field of gene therapy, they have achieved promising results and almost 40 cell and gene therapy products already in the market. In 2019, the approval of Kymriah, a chimeric antigen receptor (CAR-T) for the treatment of B-cell acute lymphoblastic leukemia, sparked the attention to Lentiviral vectors (LVs). In the following years, LVs have become one of the workhorses for the treatment of monogenic disorders and adoptive cell therapies with seven LVs-based products launched on the market. In fact, LVs are a remarkable subclass of the Retroviridae family, with the ability to integrate the genome of proliferating and non-proliferating cells and presenting lower Insertional mutagenesis when compared with γ-retrovirus.
- Leveraging single cell analysis and genetic engineering to enhance recombinant AAV production in insect cellsPublication . Virgolini, Nikolaus; Alves, Paula; Roldão, António; Isidro, Inês"The insect cell-baculovirus expression vector system (IC-BEVS) has been established as an important platform for the manufacturing of therapeutical products, including vectors for gene therapy such as recombinant adeno-associated virus (rAAV). Nevertheless, further characterisation of the underlying biological mechanisms of the IC-BEVS as well as improved engineering strategies are needed to further leverage this system towards optimal product titers and quality. In this thesis, transcriptome analysis approaches (bulk and single-cell) were applied to understand the impact on Sf9 cells of a dual baculovirus co-infection process to produce rAAV. In addition, an improved CRISPR-Cas9 delivery and gene knockout strategy was established to enhance the efficiency of target gene knockout in IC-BEVS."
- Single-cell RNA sequencing for deciphering key biological mechanisms of insect cells during influenza HA-VLPs productionPublication . Silvano, Marco; Alves, Paula; Roldão, António"The use of the Insect Cell - Baculovirus Expression Vector System (IC-BEVS) as alternative to other cell-based expression systems has increased thanks to its continued development, both as research tool and manufacturing platform. However, titers achieved are occasionally low, thus bioprocess engineering is critical to improve process performance. The comprehensive knowledge of the host cell transcriptome, mainly during infection phase, can provide clues about which molecular signatures are correlated with highly producing cells, ultimately aiding the development of rational cell line optimization strategies. In this thesis, a thorough transcriptome analysis and characterization of the IC-BEVS system was done to decipher key biological mechanisms of insect High Five cells during influenza virus-like particles (VLPs) production, highlighting the physiological determinants that contribute to increased productivity."
- Integrated continuos manufaturing of adeno-associated virusPublication . Mendes, João P.; Peixoto, Cristina; Silva, Ricardo"Adeno-associated viruses (AAV) constitute one of the most explored vectors in gene therapy for their safety, long-term expression, ability to transduce differentiated cells, and tropism. Depending on the disease targeted, AAV- based therapies can be associated with high vector demands impelling the development of processing strategies to supply the required doses. The main challenges reported include low titers generated, the quality of the product, high process volumes, equipment footprint, and the time frames associated with producing such high vector quantities.(...)"
- Advancing liver stage malaria in vitro models for drug discoveryPublication . Arez, Francisca; Alves, Paula M.; Prudêncio, Miguel"The malaria drug pipeline has been highly affected by the fastdeveloping rate of Plasmodium resistance to the currently available drugs. There are two promising and complementary approaches being explored to mitigate drug resistance. One is focused on the drugs, and includes the development of drugs exploiting novel targets and the combination of drug partners presenting the same pharmacokinetic properties but distinct modes of action. The other approach is to explore the life cycle of the parasite and target the hepatic stage of the Plasmodium life cycle.(...)"
- Harnessing complex metabolic signatures to predict drug efficacy in ovarian cancerPublication . Mendes, Ana Rita Soares; Isidro, Inês; Brito, Catarina"Ovarian carcinoma (OvC) is the most lethal gynecologic malignancy. Unfortunately, most cases are diagnosed at the later stages of the disease, impacting patient outcomes, resulting in a 5-year survival rate of less than 40%. The standard-of-care (SOC) treatment consists of cytoreduction surgery for tumor debulking and adjuvant chemotherapy, comprising a combination of platinum (cisplatin or carboplatin) with taxane (paclitaxel or docetaxel) agents.(...)"
- Atypical culture conditions and process intensification to enhance vaccine production using insect cellsPublication . Correia, Ricardo; Roldão, António; Carrondo, Manuel"Prophylactic vaccination still remains the most efficient measure of counteracting the spread of infectious diseases and attenuating their symptoms. Important advancements have been made over the years to improve the load of vaccines manufactured. Nevertheless, the emergence of novel viruses and virus strains demands the continued development of improved platforms of vaccine production, purification, and storage."
- «
- 1 (current)
- 2
- 3
- »