- Email: [email protected]
Unlocking Marine Biotechnology in the Developing World
Science & Society
Unlocking Marine Biotechnology in the Developing World Cristiane C. Thompson,1,* Ricardo H. Kruger,2 and Fabiano L. Thompson1,* Fulfilling the promise of marine biotechnology as a source for environmental and biomedical applications remains challenging. New technologies will be necessary to harness marine biodiversity, and collaboration across government, academic, and private sectors will be crucial to create mechanisms of technology transfer and promote the development of new marine biotechnology companies. The Potential Economic and Societal Benefits of Marine Biotechnology Marine biotechnology is the industrial, medical, or environmental application of biological resources from the sea. The global market for marine-derived pharmaceuticals, for example, is around US$ 5 billion. However, despite promising discoveries such as of the cephalosporinproducing fungus in 1948 at the Sardinian coast, few drugs derived from marine biodiversity have been approved, even though marine invertebrates have proved to be good sources of biologically active secondary metabolites. Examples include trabectedin (Yondelis1, an antitumor drug derived from the Caribbean sea squirt), vidarabine (an antiviral drug derived from a marine sponge), cytarabine (Ara-C, an antileukemia agent derived from sponge), and ziconotide (an analgesic agent derived from the cone snail) [1]. Marine biodiversity is thus a major untapped resource, especially in countries with high endemic biodiversity.
Marine biotechnology and the developing world are especially well suited for each other. First, many developing countries have extensive and valuable marine resources (Box 1). For instance, the combined exclusive economic zones from the Philippines, Indonesia, Brazil, and Chile comprise 15.7 million km2 (or 5% of the total global ocean area). Second, the biodiversity endemic to developing countries (e.g., in corals, sponges, and fish) is great, even though the harnessing of these biological resources remains limited. Finally, agriculture and livestock production represent a significant percentage of the gross domestic product (GDP) in developing countries. These activities have improved tremendously owing to the development and incorporation of advanced biotechnology. For example, agriculture and livestock account for 23% of the GDP of Brazil (US$ 400 billion). The value of agriculture and livestock production is a combination of advanced biotechnology, geography, and receptor capacity; food production through aquaculture represents a major branch of development in marine biotechnology.
some developing countries; for instance, aquaculture in Chile, Indonesia, and the Philippines accounts for 2 million tons of seafood yearly (33% of world annual production) [2]. Thailand is the world leader in shrimp production (300 000 tons/year, comprising 50% of world production), and Indonesia is the world leader in seaweed production (10 million tons/year, comprising 37% of the world production). Some Latin American countries, for example Argentina and Brazil, are well positioned for sustainable aquaculture development because they have large exclusive economic zones (2 million km2 and 4.5 million km2, respectively) and well-developed biotechnological infrastructure. However, one important challenge facing aquaculture remains social and environmental sustainability (durability).
Similarly, Saudi Arabia, one of the fastestgrowing economies in the world, has invested heavily in marine biotechnology discovery and development in search of economic diversification, specifically in the fields of algae biorefining, algae bioactive compounds, omics (genomics, transcriptomics, proteomics, metabolomics), and ecology. Secondary metaboLeveraging Aquaculture and lites from the seaweed Laurencia are of Bioprospecting Seafood production (in aquaculture and interest in marine biotechnology as an fisheries) offers a significant advantage to antifouling compound. Box 1. Worldwide Applications of Marine Biotechnology Asian countries are moving from traditional aquaculture to molecular aquaculture to develop vaccines (e.g., for fish and shellfish), biosensors (e.g., to monitor water quality), bioremediation, genomics, genetic manipulation to improve disease resistance, productivity, and nutritional quality. To address the issue of sustainable aquaculture, Thailand has developed shrimp omics techniques and shrimp disease diagnostics [9]. Transcriptomic analysis of seaweeds has revealed a repertoire of genes related to the production of diverse terpenes [10,11]. Elatol is one of the most relevant terpenes produced by Laurencia. Heterologous production offers a new avenue for industrial production, as demonstrated by the production of cycloartenol from Laurencia using a simple yeast fermentation method [12]. A new Pseudovibrio species that produces the antitumor compound fistularin-3 was isolated from the endemic marine sponge Aresnosclera brasiliensis. Secondary metabolites from novel Pseudovibrio isolates showed strong antimicrobial activity against bacteria [13]. Biodiversity resource conservation is an important factor for sustainable biotechnology development. Recent studies on the Abrolhos reefs in Brazil modeled the flows of energy and carbon in healthy and impacted reefs [14]. Healthier reefs have higher coral cover, higher fish biomass, and lower microbial metabolism [15]. A trophic model based on the benthic and planktonic primary production was able to predict the observed relative fish biomass of healthy reefs.
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Box 1 gives further examples of marine efficiency of discovering and producing biotechnology applications from around new products. the world. The Organization for Economic CooperaRoadblocks to Further tion and Development (OECD) innovation Development strategy recognizes the impact that fully Although global biotechnology generates functioning knowledge networks can 50 billion dollars per year, marine bio- have on marine biotechnology, both stimtechnology has clearly lagged, particu- ulating innovation and improving its effilarly in the developing world, and ciency by reducing transaction costs [5]. fulfilling the promise of marine biotech- Examples of functional networks include nology in environmental and biomedical the Joint Programming Initiative (JPI), the applications remains challenging [3]. EU ERA-NET (European Research Area Several issues hamper bioeconomic Networks) scheme, the Mediterranean development in developing countries, Science Commission (CIESM), the Euromainly the lack of investment, infrastruc- pean Marine Biological Resource Centre ture, and human capital, as well as poor (EMBRC), the Red Sea Research Centre cyber-infrastructure. Other local and at KAUST (King Abdullah University of global challenges facing marine biotech- Science and Technology), and BioMarks. nology include pollution, global warming, The OECD also argues that international the unregulated use of marine resources megaprojects are needed for harnessing (e.g., oil, gas, mining, and fisheries), and marine biodiversity, given the type and extractivism. volume of information that is required to enable the field.
Research Collaborations Across Governments and Stakeholders in the Innovation Systems Marine biotechnology uses advanced technologies, frequently new ones, in the context of interorganization collaborations (e.g., drug discovery, nutraceuticals, aquaculture, and diagnostics tools). Research collaborations for new technology sharing (such as MALDI-TOF mass spectrometry for proteomics, culturomics, metagenomics, and robotics) are urgently needed in developing countries. These new technologies could be used in model and non-model organisms (e.g., Cobia, Laurencia, Pseudovibrio, sponges, corals, and cyanobacteria) to discover new products and/or improve productivity. In addition, collaborations across government, academic, and private sectors are fundamental to create mechanisms of technology transfer and promote the development of new marine biotechnology companies. Efforts in developing countries should be linked to European initiatives [4] and other international initiatives such as those in the USA, China, and Japan to increase the
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Furthermore, marine biotechnology can build on projects such as the Census of Marine Life, a 10 year project costing US$ 650 million that involved researchers from more than 80 countries. Census bioprospecting projects have contributed greatly to our understanding of the diversity, distribution, and abundance of marine life in various habitats, and have catalogued more than 1200 new species, culminating in a landmark collection of papers describing marine biodiversity. Viral biodiversity remains an open area for bioprospecting; for example, virus bioprospecting in the South Atlantic Brazilian coast recently discovered new viral lineages [6].
countries, such as Brazil. To address this problem, the open-access Brazilian Marine Biodiversity Database (BaMBa) was developed to provide academia, industry, and environmental protection and regulatory agencies with access to marine environmental information [7]. Datasets obtained from integrated studies comprising geophysics, physicochemical studies, DNA barcoding, omics, microbiology, and imaging of benthic and fish surveys can be deposited, allowing rapid retrieval of information from any geographic location. This database is a crucial instrument for modeling, spatial planning, and economic use of the marine environment in Brazil, such as the Great Amazon Reef [8].
Concluding Remarks Investment, infrastructure, and human capital are crucial factors to boost marine biotechnology in developing countries. For instance, exploring understudied environments (e.g., deep sea hydrothermal vents, mesophotic reef regions) for the discovery of new bioactive molecules depends on expensive cutting-edge technology. Actions for the future should include the creation of new academic institutes and networks devoted to marine biotechnology. Academia should also promote marine biotechnology through technological, undergraduate, and graduate courses, as well as technological projects. To accelerate the process of discovery and technology transfer, efficient legal frameworks are needed. The success of academic incubators and startups will rely on high-quality science, protectable intellectual property, products/processes/services that are new or better than those currently available, team trust, and an accredited business model.
Durable environmental management and good governance practice are crucial for the development of marine biotechnology. To support marine biotechnology research, cyber-infrastructures must be Acknowledgments developed to acquire, manage, and store The authors thank the Ministério da Ciência, Tecnoenormous datasets. This will be a chal- logia, Inovações e Comunicações (MCTIC), the lenging task considering the large eco- Conselho Nacional de Desenvolvimento Científico nomic exclusive zones of some e Tecnológico (CNPQ), the Coordenação de
Trends in Biotechnology, December 2017, Vol. 35, No. 12
Aperfeiçoamento de Pessoal de Nível Superio (CAPES), and the Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) for financial support.
1
Institute of Biology and Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering (SAGE/COPPE), Federal University of Rio de Janeiro (UFRJ), Brazil 2 Institute of Biology, University of Brasilia (UNB), Brazil *Correspondence: [email protected] (C.C. Thompson) and [email protected] (F.L. Thompson). http://dx.doi.org/10.1016/j.tibtech.2017.08.005 References 1. Kim, S.K. and Venkatesan, J. (2015) Introduction to marine biotechnology. In Springer Handbook of Marine Biotechnology (Kim, S.K., ed.), pp. 1–8, Springer 2. FAO (2016) The State of World Fisheries and Aquaculture. Contributing to Food Security and Nutrition for All, Food and Agriculture Organization of the UN 3. Colwell, R. (2002) Marine Biotechnology in the TwentyFirst Century: Problems, Promise, and Products, National Research Council (US) Committee on Marine Biotechnology 4. Glöckner, F.O. et al. (2012) Marine Microbial Diversity and Its Role in Ecosystem Functioning and Environmental Change (Marine Board Position Paper 17), Marine Board-ESF 5. OECD (2013) Marine Biotechnology: Enabling Solutions for Ocean Productivity and Sustainability, OECD Publishing 6. Coutinho, F. et al. (2017) Marine viruses discovered via metagenomics shed light on viral strategies throughout the oceans. Nat. Commun. 8, 15955 7. Meirelles, P.M. et al. (2015) BaMBa: towards the integrated management of Brazilian marine environmental data. Database 2015, bav088 8. Moura, R.L. et al. (2016) An extensive reef system at the Amazon River mouth. Sci. Adv. 2, e1501252 9. Stentiford, G.D. et al. (2017) New paradigms to help solve the global aquaculture disease crisis. PLoS Pathog. 13, e1006160 10. Oliveira, L.S. et al. (2012) Transcriptomic analysis of the red seaweed Laurencia dendroidea (Florideophyceae, Rhodophyta) and its microbiome. BMC Genomics 13, 487 11. Oliveira, L.S. et al. (2015) New Insights on the terpenome of the redseaweed Laurencia dendroidea (Florideophyceae, Rhodophyta). Mar Drugs 13, 879–902 12. Calegario, G. et al. (2016) Cloning and functional characterization of cycloartenolsynthase from the red seaweed Laurenciadendroidea. PLoS One 11, e0165954 13. Nicacio, K.J. et al. (2017) Cultures of the marine bacterium Pseudovibrio denitrificans Ab134 produce bromotyrosinederived alkaloids previously only isolated from marine sponges. J. Nat. Prod. 80, 235–240 14. Silveira, C.B. et al. (2017) Microbial processes driving coral reef organic carbon flow. FEMS Microbiol. Rev. Published online May 9, 2017. http://dx.doi.org/10.1093/femsre/ fux018 15. Garcia, G.D. et al. (2016) Metaproteomics reveals metabolic transitions between healthy and diseased stony coral Mussismilia braziliensis. Mol. Ecol. 25, 4632–4644
Letter
Organic Nanoparticle-Based Combinatory Approaches for Gene Therapy Brahma N. Singh,1,* Prateeksha,1 Vijai K. Gupta,2,* Jieyin Chen,3 and Atanas G. Atanasov4,5 Engineered organic nanoparticle (ONP)-mediated co-delivery of genes and therapeutic agents is emerging as a powerful tool in the treatment of several genetic and non-genetic disorders. The ONP-based combinatory approach provides a technological platform that delivers genes with chemo/ radio/photo/immunotherapies for the prevention or treatment of disease progression. In a recent review, Wong and colleagues discussed a promising strategy to implement nanotechnology for gene delivery to treat cancer [1]. They described the properties of ONPs and overviewed in vitro and preclinical investigations of ONPs from the past few years with the potential to overcome the existing barriers that discourage translation of clinical trials. There is considerable current interest in the clinical application of combinatory approaches to deliver genes with chemo/radio/photodynamic/ immunotherapies [2]. Combining those ideas, we propose ONP-based combination approaches for gene therapy in humans and describe emerging approaches to promote clinical applications of ONPs in gene and drug delivery (Figure 1). The proposed nanoassembly contains gene-loaded ONPs linking drugs with different modes of action, including cytotoxic agents with cytostatic
anticancer compounds, antimetastatic agents, or biotherapies (e.g., antibodies) [3]. In contrast to viral gene delivery systems, ONPs are sparingly oncogenic or toxic, less immunogenic, easy to fabricate on a large scale, and versatile with surface modifications [4]. Moreover, ONPs have demonstrated remarkable properties such as the ability to target specific tissues or cells, protect target genes against nuclease degradation, improve DNA stability, and enhance transformation efficiency. By contrast, inorganic NPs are less promising for gene therapy because of their potential toxicity [5]. Thus, ONPs have many desirable properties that could make them ideal carrier tools for combinatory approaches to treat cancer and other diseases.
Developing ONP-Based Combinatory Therapeutics Although many studies have identified vectors in the intracellular delivery of genes and therapeutic drugs, their low transfection efficiency and poor performance are major bottlenecks. However, the emergence of nanotechnology in recent years has suggested ONPs as promising non-viral vectors for gene delivery [5–7]. ONPs have special features, such as improved circulation and reduced toxicity, that can make them ideal for loading with genes or chemotherapy drugs [8]. Many anticancer drugs suffer from dose-dependent toxicity. To overcome these toxic effects, liposome ONPs linked to wild-type tumor suppressor gene p53 plasmid DNA, antitransferrin receptor single-chain antibody fragment, and temozolomide (enhancing the antitumor action) have shown promise in Phase II studies [9]. Likewise, research on treating colon cancer with a combination therapy of camptothecin-conjugated multilayered polymer ONPs, loaded with the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene, and doxorubicin has also attracted attention [10]. Finally, co-delivery of paclitaxel and a
Trends in Biotechnology, December 2017, Vol. 35, No. 12
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Unlocking Marine Biotechnology in the Developing World Cristiane C. Thompson,1,* Ricardo H. Kruger,2 and Fabiano L. Thompson1,* Fulfilling the promise of marine biotechnology as a source for environmental and biomedical applications remains challenging. New technologies will be necessary to harness marine biodiversity, and collaboration across government, academic, and private sectors will be crucial to create mechanisms of technology transfer and promote the development of new marine biotechnology companies. The Potential Economic and Societal Benefits of Marine Biotechnology Marine biotechnology is the industrial, medical, or environmental application of biological resources from the sea. The global market for marine-derived pharmaceuticals, for example, is around US$ 5 billion. However, despite promising discoveries such as of the cephalosporinproducing fungus in 1948 at the Sardinian coast, few drugs derived from marine biodiversity have been approved, even though marine invertebrates have proved to be good sources of biologically active secondary metabolites. Examples include trabectedin (Yondelis1, an antitumor drug derived from the Caribbean sea squirt), vidarabine (an antiviral drug derived from a marine sponge), cytarabine (Ara-C, an antileukemia agent derived from sponge), and ziconotide (an analgesic agent derived from the cone snail) [1]. Marine biodiversity is thus a major untapped resource, especially in countries with high endemic biodiversity.
Marine biotechnology and the developing world are especially well suited for each other. First, many developing countries have extensive and valuable marine resources (Box 1). For instance, the combined exclusive economic zones from the Philippines, Indonesia, Brazil, and Chile comprise 15.7 million km2 (or 5% of the total global ocean area). Second, the biodiversity endemic to developing countries (e.g., in corals, sponges, and fish) is great, even though the harnessing of these biological resources remains limited. Finally, agriculture and livestock production represent a significant percentage of the gross domestic product (GDP) in developing countries. These activities have improved tremendously owing to the development and incorporation of advanced biotechnology. For example, agriculture and livestock account for 23% of the GDP of Brazil (US$ 400 billion). The value of agriculture and livestock production is a combination of advanced biotechnology, geography, and receptor capacity; food production through aquaculture represents a major branch of development in marine biotechnology.
some developing countries; for instance, aquaculture in Chile, Indonesia, and the Philippines accounts for 2 million tons of seafood yearly (33% of world annual production) [2]. Thailand is the world leader in shrimp production (300 000 tons/year, comprising 50% of world production), and Indonesia is the world leader in seaweed production (10 million tons/year, comprising 37% of the world production). Some Latin American countries, for example Argentina and Brazil, are well positioned for sustainable aquaculture development because they have large exclusive economic zones (2 million km2 and 4.5 million km2, respectively) and well-developed biotechnological infrastructure. However, one important challenge facing aquaculture remains social and environmental sustainability (durability).
Similarly, Saudi Arabia, one of the fastestgrowing economies in the world, has invested heavily in marine biotechnology discovery and development in search of economic diversification, specifically in the fields of algae biorefining, algae bioactive compounds, omics (genomics, transcriptomics, proteomics, metabolomics), and ecology. Secondary metaboLeveraging Aquaculture and lites from the seaweed Laurencia are of Bioprospecting Seafood production (in aquaculture and interest in marine biotechnology as an fisheries) offers a significant advantage to antifouling compound. Box 1. Worldwide Applications of Marine Biotechnology Asian countries are moving from traditional aquaculture to molecular aquaculture to develop vaccines (e.g., for fish and shellfish), biosensors (e.g., to monitor water quality), bioremediation, genomics, genetic manipulation to improve disease resistance, productivity, and nutritional quality. To address the issue of sustainable aquaculture, Thailand has developed shrimp omics techniques and shrimp disease diagnostics [9]. Transcriptomic analysis of seaweeds has revealed a repertoire of genes related to the production of diverse terpenes [10,11]. Elatol is one of the most relevant terpenes produced by Laurencia. Heterologous production offers a new avenue for industrial production, as demonstrated by the production of cycloartenol from Laurencia using a simple yeast fermentation method [12]. A new Pseudovibrio species that produces the antitumor compound fistularin-3 was isolated from the endemic marine sponge Aresnosclera brasiliensis. Secondary metabolites from novel Pseudovibrio isolates showed strong antimicrobial activity against bacteria [13]. Biodiversity resource conservation is an important factor for sustainable biotechnology development. Recent studies on the Abrolhos reefs in Brazil modeled the flows of energy and carbon in healthy and impacted reefs [14]. Healthier reefs have higher coral cover, higher fish biomass, and lower microbial metabolism [15]. A trophic model based on the benthic and planktonic primary production was able to predict the observed relative fish biomass of healthy reefs.
Trends in Biotechnology, December 2017, Vol. 35, No. 12
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Box 1 gives further examples of marine efficiency of discovering and producing biotechnology applications from around new products. the world. The Organization for Economic CooperaRoadblocks to Further tion and Development (OECD) innovation Development strategy recognizes the impact that fully Although global biotechnology generates functioning knowledge networks can 50 billion dollars per year, marine bio- have on marine biotechnology, both stimtechnology has clearly lagged, particu- ulating innovation and improving its effilarly in the developing world, and ciency by reducing transaction costs [5]. fulfilling the promise of marine biotech- Examples of functional networks include nology in environmental and biomedical the Joint Programming Initiative (JPI), the applications remains challenging [3]. EU ERA-NET (European Research Area Several issues hamper bioeconomic Networks) scheme, the Mediterranean development in developing countries, Science Commission (CIESM), the Euromainly the lack of investment, infrastruc- pean Marine Biological Resource Centre ture, and human capital, as well as poor (EMBRC), the Red Sea Research Centre cyber-infrastructure. Other local and at KAUST (King Abdullah University of global challenges facing marine biotech- Science and Technology), and BioMarks. nology include pollution, global warming, The OECD also argues that international the unregulated use of marine resources megaprojects are needed for harnessing (e.g., oil, gas, mining, and fisheries), and marine biodiversity, given the type and extractivism. volume of information that is required to enable the field.
Research Collaborations Across Governments and Stakeholders in the Innovation Systems Marine biotechnology uses advanced technologies, frequently new ones, in the context of interorganization collaborations (e.g., drug discovery, nutraceuticals, aquaculture, and diagnostics tools). Research collaborations for new technology sharing (such as MALDI-TOF mass spectrometry for proteomics, culturomics, metagenomics, and robotics) are urgently needed in developing countries. These new technologies could be used in model and non-model organisms (e.g., Cobia, Laurencia, Pseudovibrio, sponges, corals, and cyanobacteria) to discover new products and/or improve productivity. In addition, collaborations across government, academic, and private sectors are fundamental to create mechanisms of technology transfer and promote the development of new marine biotechnology companies. Efforts in developing countries should be linked to European initiatives [4] and other international initiatives such as those in the USA, China, and Japan to increase the
1120
Furthermore, marine biotechnology can build on projects such as the Census of Marine Life, a 10 year project costing US$ 650 million that involved researchers from more than 80 countries. Census bioprospecting projects have contributed greatly to our understanding of the diversity, distribution, and abundance of marine life in various habitats, and have catalogued more than 1200 new species, culminating in a landmark collection of papers describing marine biodiversity. Viral biodiversity remains an open area for bioprospecting; for example, virus bioprospecting in the South Atlantic Brazilian coast recently discovered new viral lineages [6].
countries, such as Brazil. To address this problem, the open-access Brazilian Marine Biodiversity Database (BaMBa) was developed to provide academia, industry, and environmental protection and regulatory agencies with access to marine environmental information [7]. Datasets obtained from integrated studies comprising geophysics, physicochemical studies, DNA barcoding, omics, microbiology, and imaging of benthic and fish surveys can be deposited, allowing rapid retrieval of information from any geographic location. This database is a crucial instrument for modeling, spatial planning, and economic use of the marine environment in Brazil, such as the Great Amazon Reef [8].
Concluding Remarks Investment, infrastructure, and human capital are crucial factors to boost marine biotechnology in developing countries. For instance, exploring understudied environments (e.g., deep sea hydrothermal vents, mesophotic reef regions) for the discovery of new bioactive molecules depends on expensive cutting-edge technology. Actions for the future should include the creation of new academic institutes and networks devoted to marine biotechnology. Academia should also promote marine biotechnology through technological, undergraduate, and graduate courses, as well as technological projects. To accelerate the process of discovery and technology transfer, efficient legal frameworks are needed. The success of academic incubators and startups will rely on high-quality science, protectable intellectual property, products/processes/services that are new or better than those currently available, team trust, and an accredited business model.
Durable environmental management and good governance practice are crucial for the development of marine biotechnology. To support marine biotechnology research, cyber-infrastructures must be Acknowledgments developed to acquire, manage, and store The authors thank the Ministério da Ciência, Tecnoenormous datasets. This will be a chal- logia, Inovações e Comunicações (MCTIC), the lenging task considering the large eco- Conselho Nacional de Desenvolvimento Científico nomic exclusive zones of some e Tecnológico (CNPQ), the Coordenação de
Trends in Biotechnology, December 2017, Vol. 35, No. 12
Aperfeiçoamento de Pessoal de Nível Superio (CAPES), and the Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) for financial support.
1
Institute of Biology and Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering (SAGE/COPPE), Federal University of Rio de Janeiro (UFRJ), Brazil 2 Institute of Biology, University of Brasilia (UNB), Brazil *Correspondence: [email protected] (C.C. Thompson) and [email protected] (F.L. Thompson). http://dx.doi.org/10.1016/j.tibtech.2017.08.005 References 1. Kim, S.K. and Venkatesan, J. (2015) Introduction to marine biotechnology. In Springer Handbook of Marine Biotechnology (Kim, S.K., ed.), pp. 1–8, Springer 2. FAO (2016) The State of World Fisheries and Aquaculture. Contributing to Food Security and Nutrition for All, Food and Agriculture Organization of the UN 3. Colwell, R. (2002) Marine Biotechnology in the TwentyFirst Century: Problems, Promise, and Products, National Research Council (US) Committee on Marine Biotechnology 4. Glöckner, F.O. et al. (2012) Marine Microbial Diversity and Its Role in Ecosystem Functioning and Environmental Change (Marine Board Position Paper 17), Marine Board-ESF 5. OECD (2013) Marine Biotechnology: Enabling Solutions for Ocean Productivity and Sustainability, OECD Publishing 6. Coutinho, F. et al. (2017) Marine viruses discovered via metagenomics shed light on viral strategies throughout the oceans. Nat. Commun. 8, 15955 7. Meirelles, P.M. et al. (2015) BaMBa: towards the integrated management of Brazilian marine environmental data. Database 2015, bav088 8. Moura, R.L. et al. (2016) An extensive reef system at the Amazon River mouth. Sci. Adv. 2, e1501252 9. Stentiford, G.D. et al. (2017) New paradigms to help solve the global aquaculture disease crisis. PLoS Pathog. 13, e1006160 10. Oliveira, L.S. et al. (2012) Transcriptomic analysis of the red seaweed Laurencia dendroidea (Florideophyceae, Rhodophyta) and its microbiome. BMC Genomics 13, 487 11. Oliveira, L.S. et al. (2015) New Insights on the terpenome of the redseaweed Laurencia dendroidea (Florideophyceae, Rhodophyta). Mar Drugs 13, 879–902 12. Calegario, G. et al. (2016) Cloning and functional characterization of cycloartenolsynthase from the red seaweed Laurenciadendroidea. PLoS One 11, e0165954 13. Nicacio, K.J. et al. (2017) Cultures of the marine bacterium Pseudovibrio denitrificans Ab134 produce bromotyrosinederived alkaloids previously only isolated from marine sponges. J. Nat. Prod. 80, 235–240 14. Silveira, C.B. et al. (2017) Microbial processes driving coral reef organic carbon flow. FEMS Microbiol. Rev. Published online May 9, 2017. http://dx.doi.org/10.1093/femsre/ fux018 15. Garcia, G.D. et al. (2016) Metaproteomics reveals metabolic transitions between healthy and diseased stony coral Mussismilia braziliensis. Mol. Ecol. 25, 4632–4644
Letter
Organic Nanoparticle-Based Combinatory Approaches for Gene Therapy Brahma N. Singh,1,* Prateeksha,1 Vijai K. Gupta,2,* Jieyin Chen,3 and Atanas G. Atanasov4,5 Engineered organic nanoparticle (ONP)-mediated co-delivery of genes and therapeutic agents is emerging as a powerful tool in the treatment of several genetic and non-genetic disorders. The ONP-based combinatory approach provides a technological platform that delivers genes with chemo/ radio/photo/immunotherapies for the prevention or treatment of disease progression. In a recent review, Wong and colleagues discussed a promising strategy to implement nanotechnology for gene delivery to treat cancer [1]. They described the properties of ONPs and overviewed in vitro and preclinical investigations of ONPs from the past few years with the potential to overcome the existing barriers that discourage translation of clinical trials. There is considerable current interest in the clinical application of combinatory approaches to deliver genes with chemo/radio/photodynamic/ immunotherapies [2]. Combining those ideas, we propose ONP-based combination approaches for gene therapy in humans and describe emerging approaches to promote clinical applications of ONPs in gene and drug delivery (Figure 1). The proposed nanoassembly contains gene-loaded ONPs linking drugs with different modes of action, including cytotoxic agents with cytostatic
anticancer compounds, antimetastatic agents, or biotherapies (e.g., antibodies) [3]. In contrast to viral gene delivery systems, ONPs are sparingly oncogenic or toxic, less immunogenic, easy to fabricate on a large scale, and versatile with surface modifications [4]. Moreover, ONPs have demonstrated remarkable properties such as the ability to target specific tissues or cells, protect target genes against nuclease degradation, improve DNA stability, and enhance transformation efficiency. By contrast, inorganic NPs are less promising for gene therapy because of their potential toxicity [5]. Thus, ONPs have many desirable properties that could make them ideal carrier tools for combinatory approaches to treat cancer and other diseases.
Developing ONP-Based Combinatory Therapeutics Although many studies have identified vectors in the intracellular delivery of genes and therapeutic drugs, their low transfection efficiency and poor performance are major bottlenecks. However, the emergence of nanotechnology in recent years has suggested ONPs as promising non-viral vectors for gene delivery [5–7]. ONPs have special features, such as improved circulation and reduced toxicity, that can make them ideal for loading with genes or chemotherapy drugs [8]. Many anticancer drugs suffer from dose-dependent toxicity. To overcome these toxic effects, liposome ONPs linked to wild-type tumor suppressor gene p53 plasmid DNA, antitransferrin receptor single-chain antibody fragment, and temozolomide (enhancing the antitumor action) have shown promise in Phase II studies [9]. Likewise, research on treating colon cancer with a combination therapy of camptothecin-conjugated multilayered polymer ONPs, loaded with the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene, and doxorubicin has also attracted attention [10]. Finally, co-delivery of paclitaxel and a
Trends in Biotechnology, December 2017, Vol. 35, No. 12
1121