704/DNA vaccines leverage cytoplasmic DNA stimulation to promote anti-HIV neutralizing antibody production in mice and strong immune response against alpha-fetoprotein in non-human primates.

Genetic immunization is an attractive approach for prophylactic and therapeutic vaccination using synthetic vectors to deliver antigen-encoding nucleic acids. Recently, DNA delivered by a physical means or RNA by liposomes consisting of four different lipids demonstrated good protection in human phase III clinical trials and received Drugs Controller General of India and US FDA approval to protect against COVID-19, respectively. However, the development of a system allowing for efficient and simple delivery of nucleic acids while improving immune response priming has the potential to unleash the full therapeutic potential of genetic immunization. DNA-based gene therapies and vaccines have the potential for rapid development, as exemplified by the recent approval of Collategene, a gene therapy to treat human critical limb ischemia, and ZyCoV, a DNA vaccine delivered by spring-powered jet injector to protect against SARS-CoV2 infection. Recently, we reported amphiphilic block copolymer 704 as a promising synthetic vector for DNA vaccination in various models of human diseases. This vector allows dose sparing of antigen-encoding plasmid DNA. Here, we report the capacity of 704-mediated HIV and anti-hepatocellular carcinoma DNA vaccines to induce the production of specific antibodies against gp120 HIV envelope proteins in mice and against alpha-fetoprotein antigen in non-human primates, respectively. An investigation of the underlying mechanisms showed that 704-mediated vaccination did trigger a strong immune response by (1) allowing a direct DNA delivery into the cytosol, (2) promoting an intracytoplasmic DNA sensing leading to both interferon and NF-κB cascade stimulation, and (3) inducing antigen expression by muscle cells and presentation by antigen-presenting cells, leading to the induction of a robust adaptive response. Overall, our findings suggest that the 704-mediated DNA vaccination platform is an attractive method to develop both prophylactic and therapeutic vaccines.

Electrochemical biosensors for SARS-CoV-2 detection: Voltametric or impedimetric transduction?

During the COVID-19 pandemic, electrochemical biosensors have shown several advantages including accuracy, low cost, possibility of miniaturization and portability, which make them an interesting testing method for rapid point-of-care (POC) detection of SARS-CoV-2 infection, allowing the detection of both viral RNA and viral antigens. Herein, we reviewed advancements in electrochemical biosensing platforms towards the detection of SARS-CoV-2 based on voltametric and impedimetric transduction modes, highlighting the advantages and drawbacks of the two methods.

Ultrasensitive PCR-Free detection of whole virus genome by electrochemiluminescence.

Detection of nucleic acids is crucial in many medical applications, and in particular for monitoring infectious diseases, as it has become perfectly clear after the pandemic infection of COVID-19. In this context, the development of innovative detection methods based on signal-amplification rather than analyte-amplification represents a significant breakthrough compared to existing PCR-based methodologies, allowing the development of new nucleic acid detection technologies suitable to be integrated in portable and low-cost sensor devices while keeping high sensitivities, thus enabling massive diagnostic screening. In this work, we present a novel molecular sensor for the ultrasensitive PCR-free detection of Hepatitis B Virus (HBV) based on electrochemiluminescence (ECL). Thanks to the combination of surface cooperative hybridization scheme with ECL detection strategy, our novel DNA sensor is able to detect HBV genome - both synthetic and extracted - with the unprecedented limit of detection (LoD) of 0.05 cps µL-1 for extracted sample, that is even lower than the typical LoD of PCR methodologies. The detection concept presented here for HBV detection is very versatile and can be extended to other pathogens, paving the way for future development of rapid molecular test for infectious diseases, both viral and bacterial, in Point-of-Care (PoC) format.

Nanobiosensors as new diagnostic tools for SARS, MERS and COVID-19: from past to perspectives.

The severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and novel coronavirus 19 (COVID-19) epidemics represent the biggest global health threats in the last two decades. These infections manifest as bronchitis, pneumonia or severe, sometimes fatal, respiratory illness. The novel coronavirus seems to be associated with milder infections but it has spread globally more rapidly becoming a pandemic. This review summarises the state of the art of nanotechnology-based affinity biosensors for SARS, MERS and COVID-19 detection. The nanobiosensors are antibody- or DNA-based biosensors with electrochemical, optical or FET-based transduction. Various kinds of nanomaterials, such as metal nanoparticles, nanowires and graphene, have been merged to the affinity biosensors to enhance their analytical performances. The advantages of the use of the nanomaterials are highlighted, and the results compared with those obtained using non-nanostructured biosensors. A critical comparison with conventional methods, such as RT-PCR and ELISA, is also reported. It is hoped that this review will provide interesting information for the future development of new reliable nano-based platforms for point-of-care diagnostic devices for COVID-19 prevention and control.

Developments in biosensors for CoV detection and future trends.

This review summarizes the state of art of biosensor technology for Coronavirus (CoV) detection, the current challenges and the future perspectives. Three categories of affinity-based biosensors (ABBs) have been developed, depending on their transduction mechanism, namely electrochemical, optical and piezoelectric biosensors. The biorecognition elements include antibodies and DNA, which undergo important non-covalent binding interactions, with the formation of antigen-antibody and ssDNA/oligonucleotide-complementary strand complexes in immuno- and DNA-sensors, respectively. The analytical performances, the advantages and drawbacks of each type of biosensor are highlighted, discussed, and compared to traditional methods. It is hoped that this review will encourage scientists and academics to design and develop new biosensing platforms for point-of-care (POC) diagnostics to manage the coronavirus disease 2019 (COVID-19) pandemic, providing interesting reference for future studies.

DNA/RNA Electrochemical Biosensing Devices a Future Replacement of PCR Methods for a Fast Epidemic Containment.

Pandemics require a fast and immediate response to contain potential infectious carriers. In the recent 2020 Covid-19 worldwide pandemic, authorities all around the world have failed to identify potential carriers and contain it on time. Hence, a rapid and very sensitive testing method is required. Current diagnostic tools, reverse transcription PCR (RT-PCR) and real-time PCR (qPCR), have its pitfalls for quick pandemic containment such as the requirement for specialized professionals and instrumentation. Versatile electrochemical DNA/RNA sensors are a promising technological alternative for PCR based diagnosis. In an electrochemical DNA sensor, a nucleic acid hybridization event is converted into a quantifiable electrochemical signal. A critical challenge of electrochemical DNA sensors is sensitive detection of a low copy number of DNA/RNA in samples such as is the case for early onset of a disease. Signal amplification approaches are an important tool to overcome this sensitivity issue. In this review, the authors discuss the most recent signal amplification strategies employed in the electrochemical DNA/RNA diagnosis of pathogens.

Ultrasensitive detection of pathogenic viruses with electrochemical biosensor: State of the art.

Last few decades, viruses are a real menace to human safety. Therefore, the rapid identification of viruses should be one of the best ways to prevent an outbreak and important implications for medical healthcare. The recent outbreak of coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus which belongs to the single-stranded, positive-strand RNA viruses. The pandemic dimension spread of COVID-19 poses a severe threat to the health and lives of seven billion people worldwide. There is a growing urgency worldwide to establish a point-of-care device for the rapid detection of COVID-19 to prevent subsequent secondary spread. Therefore, the need for sensitive, selective, and rapid diagnostic devices plays a vital role in selecting appropriate treatments and to prevent the epidemics. During the last decade, electrochemical biosensors have emerged as reliable analytical devices and represent a new promising tool for the detection of different pathogenic viruses. This review summarizes the state of the art of different virus detection with currently available electrochemical detection methods. Moreover, this review discusses different fabrication techniques, detection principles, and applications of various virus biosensors. Future research also looks at the use of electrochemical biosensors regarding a potential detection kit for the rapid identification of the COVID-19.