Browsing by Author "Becerra, Daniela"

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    Effect of recombinant protein production and release on microalgal fitness and the impact of environmental conditions for localized therapeutic delivery
    (Springer Nature, 2025) Carvajal Díaz, Felipe Alonso; Vargas Torres, Valentina Isabel; Becerra, Daniela; González Quezada, Nicolás Marcelo Orlando; Egaña, José T.
    Backgroud Genetically engineered photosynthetic microorganisms have been proposed as a therapeutic approach for the localized delivery of oxygen and recombinant proteins to tissues in various pathological conditions. However, the effect of recombinant protein production and secretion on microalgal fitness, as well as the impact of key environmental conditions on their potential therapeutic performance, has not yet been described. Therefore, in this study, the microalga Chlamydomonas reinhardtii was genetically engineered to produce and release the reporter protein mVenus and was then challenged by exposure to different media, temperatures, and substrates. Results The genetically modified microalgae were able to produce and release the mVenus protein under standard culture conditions without affecting overall fitness, including cell size and shape, growth potential, and oxygen metabolism, compared to the wild-type strain. Under mammalian cell culture conditions, the strains continued to produce and secrete mVenus protein for up to four days at 22 °C, 30 °C, and 37 °C. Additionally, photosynthetic biomaterials containing the engineered microalgae showed continuous recombinant protein release at 30 °C and 37 °C for up to four days. Conclusion The microalga Chlamydomonas reinhardtii can be genetically engineered to produce and release recombinant proteins without detrimental effects on its fitness, showing therapeutic potential under mammalian culture conditions and within biomaterials designed to promote tissue regeneration. Overall, these findings support the use of genetically engineered photosynthetic microalgae for the localized and controlled release of oxygen and recombinant proteins for several therapeutic applications.
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    Oxygenation by Intravascular Photosynthesis Reduces Kidney Damage During ex Vivo Preservation
    (2024) Veloso-Gimenez, Valentina; Cardenas-Calderon, Camila; Castillo, Valentina; Carvajal, Felipe; Gallardo-Aguero, Daniela; Gonzalez-Itier, Sergio; Corrales-Orovio, Rocio; Becerra, Daniela; Miranda, Miguel; Rebolledo, Rolando; San Martin, Sebastian; Boric, Mauricio P.; Egana, Jose Tomas
    Several clinical issues are associated with reduced oxygen delivery to tissues due to impaired vascular perfusion; moreover, organs procured for transplantation are subjected to severe hypoxia during preservation. Consequently, alternative tissue oxygenation is an active field in biomedical research where several innovative approaches have been recently proposed. Among these, intravascular photosynthesis represents a promising approach as it relies on the intrinsic capacity of certain microorganisms to produce oxygen upon illumination. In this context, this work aims at the development of photosynthetic perfusable solutions that could be applied to preserve organs for transplantation purposes. Our findings demonstrate that a biocompatible physiological solution containing the photosynthetic microalgae Chlamydomonas reinhardtii can fulfill the metabolic oxygen demand of rat kidney slices in vitro. Furthermore, intravascular administration of this solution does not induce tissue damage in the rat kidneys. Moreover, kidney slices obtained from these algae-perfused organs exhibited significantly improved preservation after 24 h of incubation in hypoxia while exposed to light, resulting in reduced tissue damage and enhanced metabolic status. Overall, the results presented here contribute to the development of alternative strategies for tissue oxygenation, supporting the use of perfusable photosynthetic solutions for organ preservation in transplantation.
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    Towards chlorocytes for therapeutic intravascular photosynthesis
    (2024) Vargas Torres Valentina Isabel; Becerra, Daniela; Boric P., Mauricio; Egaña, José T.
    Aerobic metabolism relies on external oxygen production through photosynthesis and its subsequent transport into each cell of the body via the cardiorespiratory system. This mechanism has successfully evolved over millions of years, enabling animals to inhabit most environments on Earth. However, the insufficient oxygen supply leads to several clinical problems, ranging from non-healing wounds to tumor resistance to therapy. Given that photosynthetic microorganisms are capable of producing oxygen and removing carbon dioxide from the environment, over the last decade, several groups worldwide have proposed their potential use as an alternative tissue oxygenation approach. While most studies have demonstrated safety and efficacy after local tissue administration, recent studies have also suggested that systemic administration could trigger intravascular photosynthesis. If successful, the development of a new generation of circulating cells, known as chlorocytes, may partially replace the role of erythrocytes in gas exchange within the body, without relying on external supply and vascular flow. This work reviews the existing literature on local and systemic administration of photosynthetic microorganisms, highlighting the main challenges in the field and potential solutions to unleash the enormous potential clinical impact of chlorocytes and intravascular photosynthesis. Key points: • Circulating photosynthetic microorganisms could deliver oxygen to tissues • Microalgae and cyanobacteria have shown safety and efficacy for oxygen delivery • Several key challenges need to be addressed for the clinical success of chlorocytes.