Pioneer Science’s Advanced Therapies front brings together projects that explore innovative approaches for developing new therapeutic strategies, focused on complex and difficult-to-treat diseases. By integrating biotechnology, gene editing, and advanced experimental models, the research seeks to understand pathological mechanisms and also to intervene precisely in biological processes, expanding the possibilities of translating scientific knowledge into clinical applications.
The project investigates new non-viral strategies for delivering CRISPR/Cas9 gene-editing systems, combining cell-penetrating peptides, extracellular vesicles (EVs), and programmable cellular platforms. The goal is to understand and optimize intracellular transport, endosomal escape, and cellular specificity, aiming to increase the efficiency and safety of gene editing in complex biological models. Modular architectures will be developed and tested for incorporating CRISPR into EVs, conjugating targeting peptides, and enabling controlled release of the genetic payload. The project aims to produce prototype in vivo delivery systems that are scalable and compatible with regulatory requirements, helping to make advanced gene-editing therapies more accessible and applicable in hematological and neurological diseases.
The group led by Thyago Calvo investigates the therapeutic potential of overexpressing neuroprotective factors through CRISPR-Cas9 epigenetic editing in Alzheimer’s disease.
It all begins with the understanding that the aging of the Brazilian population is associated with a rise in neurodegenerative diseases, especially Alzheimer’s. In addition to being highly complex, the disease has only a limited range of disease-modifying treatments, still restricted to patients at specific stages. An intriguing observation is that some individuals age cognitively healthy even when they carry the classical markers of the disease in the brain, such as beta-amyloid plaques and tau tangles.
What sets them apart? One hypothesis driving this project is that the brain has endogenous resilience mechanisms that compensate for or attenuate the impact of neuropathology. The group seeks to activate these neuronal resilience programs to obtain such benefits.
The project proposes using CRISPR-Cas9 epigenome editing to increase the levels of a few key neuroprotective proteins in neuronal models relevant to the disease. Unlike traditional approaches that introduce exogenous genes or inhibit protein aggregates, this strategy acts on the regulation of endogenous gene expression, without modifying DNA, in a specific, potentially reversible, and safe manner.
The neuroprotective effects of this intervention are initially being studied in vitro, in models of beta-amyloid aggregates and in neurons exposed to neurotoxic agents. If successful, this modality will represent a relevant conceptual and therapeutic advance by exploring the potential of CRISPR epigenome editing to activate endogenous programs of neuronal resilience. In addition to its strong translational potential, this new generation of advanced therapies may prove useful for other complex diseases, whether neurodegenerative or not.
The group’s studies investigate the mechanisms associated with the persistence of symptoms in infections caused by arthritogenic alphaviruses, such as Chikungunya and Mayaro. Although the acute phase of these infections is well characterized, a significant proportion of patients develop chronic arthralgia — persistent joint inflammation that can last from weeks to years and significantly impact quality of life.
Using immunocompetent murine models that reproduce the transition from the acute to the chronic phase, the research observes that even in the absence of detectable viral particles, viral RNA remains present in muscle tissues. Based on this finding, the project seeks to understand the molecular mechanisms of the immune response, RNA regulation, and the role of possible viral persistence in sustaining the chronic inflammatory state. By advancing the understanding of these processes, the research contributes to identifying new therapeutic targets for treating chronic complications associated with viral infections.
