Complex target SELEX-based identification of DNA aptamers against Bungarus caeruleus venom for the detection of envenomation using a paper-based device

Anand, Anjali; Chatterjee, Bandhan; Dhiman, Abhijeet; Goel, Renu; Khan, Eshan; Malhotra, Anita; Santra, Vishal; Salvi, Nitin; khadilkar, MV; Bhatnagar, Ira; Kumar, Amit; Asthana, Amit; Sharma, Tarun

doi:10.1016/j.bios.2021.113523

Cited by 16 publications

(7 citation statements)

References 71 publications

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“…Additional issues arise due to delayed administration of antivenom treatment 13 . Antibody 14,15,16,17,18,19,20,21,22 and non-antibody-based therapeutics 23,24,25,26,27,28,29,30 have been tested in preclinical studies, but the development of these types of molecules require either immunization of animals or development of large libraries that require extensive selection, screening, and optimization efforts 31 .…”

Section: Mainmentioning

confidence: 99%

De novo designed proteins neutralize lethal snake venom toxins

Baker,

Torres,

Valle

et al. 2024

Preprint

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Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more1,2. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage3 and inhibition of nicotinic acetylcholine receptors (nAChRs) resulting in life-threatening neurotoxicity4. Currently, the only available treatments for snakebite consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs5,6,7. Here, we use deep learning methods to de novo design proteins to bind short- and long-chain α-neurotoxins and cytotoxins from the 3FTx family. With limited experimental screening, we obtain protein designs with remarkable thermal stability, high binding affinity, and near-atomic level agreement with the computational models. The designed proteins effectively neutralize all three 3FTx sub-families in vitro and protect mice from a lethal neurotoxin challenge. Such potent, stable, and readily manufacturable toxin-neutralizing proteins could provide the basis for safer, cost-effective, and widely accessible next-generation antivenom therapeutics. Beyond snakebite, our computational design methodology should help democratize therapeutic discovery, particularly in resource-limited settings, by substantially reducing costs and resource requirements for development of therapies to neglected tropical diseases

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Section: Mainmentioning

confidence: 99%

De novo designed proteins neutralize lethal snake venom toxins

Baker,

Torres,

Valle

et al. 2024

Preprint

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show abstract

“…Several immuno- and DNA-based multiplex methods have emerged for snake venom detection 5 , 11 , including enzyme-linked immunosorbent assays (ELISAs) 12 , aptamer-linked immobilized sorbent assay (ALISA) 13 , agglutination assays 14 , optical immunoassays 15 , fluorescent sensor microarrays 16 , polymerase chain reactions 17 , loop-mediated isothermal amplifications 18 , impedimetric immunosensors 19 , and mass spectrometry 20 . However, these proof-of-concept methods are laboratory-based and require extensive time (> 2 h), dedicated equipment, and trained personnel to carry out.…”

Section: Introductionmentioning

confidence: 99%

Multiplex lateral flow assay development for snake venom detection in biological matrices

Knudsen,

Belfakir,

Degnegaard

et al. 2024

Sci Rep

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Bothrops and Lachesis are two of Brazil’s medically most relevant snake genera, causing tens of thousands of bites annually. Fortunately, Brazil has good accessibility to high-quality antivenoms at the genus and inter-genus level, enabling the treatment of many of these envenomings. However, the optimal use of these treatments requires that the snake species responsible for the bite is determined. Currently, physicians use a syndromic approach to diagnose snakebite, which can be difficult for medical personnel with limited training in clinical snakebite management. In this work, we have developed a novel monoclonal antibody-based multiplex lateral flow assay for differentiating Bothrops and Lachesis venoms within 15 min. The test can be read by the naked eye or (semi)-quantitatively by a smartphone supported by a 3D-printed attachment for controlling lighting conditions. The LFA can detect Bothrops and Lachesis venoms in spiked plasma and urine matrices at concentrations spanning six orders of magnitude. The LFA has detection limits of 10–50 ng/mL in spiked plasma and urine, and 50–500 ng/mL in spiked sera, for B. atrox and L. muta venoms. This test could potentially support medical personnel in correctly diagnosing snakebite envenomings at the point-of-care in Brazil, which may help improve patient outcomes and save lives.

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“…Aptamers are stable in complex environments and highly resistant to denaturation and degradation when modified and optimized appropriately. A biosensor that uses an aptamer as a molecular recognition element or bioreceptor is called an aptasensor ( Bezerra et al, 2019 ; Anand et al, 2021 ; Bhardwaj and Kumar Sharma, 2022 ; McKeague et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

A review of antibody, aptamer, and nanomaterials synergistic systems for an amplified electrochemical signal

Reaño,

Escobar

2024

Front. Bioeng. Biotechnol.

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The synergy between biomolecules with inorganic nanomaterials and nanoparticles has been investigated over the past years, primarily to improve biomarker reception, generate signals, and amplify the signals generated. In this paper, several articles on aptamer-based and antibody-based electrochemical biosensors that target antigens were examined. Among the key characteristics identified were the electrochemical platform development, which includes the usage of nanomaterials as electroactive or electrocatalytic labels, crosslinking of the biological agent with inorganic compounds, and electrode coating to provide an electronic source and support efficient electron transfer. A single approach using labeled or unlabeled biological receptors has become advantageous due to its simple architecture and more straightforward application method. However, the dual system approach allows the incorporation of more nanomaterials to boost the signal and add more features to the electrochemical system. The dual system approach uses a capture and reporter probe in a competitive or sandwich detection format. The reporter probe is often labeled by an electroactive or electrocatalytic compound or immobilized in a nanocarrier, resulting in an increase in measured peak current in proportion to the target’s concentration. The reported limit of detection and linear range for each platform is presented to assess its efficiency. Generally, the dual system aptasensor showed higher sensitivity, stability, and reproducibility than the immunosensor in comparable settings. The aptasensor showed promising results for the development of point-of-care type applications.

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Complex target SELEX-based identification of DNA aptamers against Bungarus caeruleus venom for the detection of envenomation using a paper-based device

Cited by 16 publications

References 71 publications

De novo designed proteins neutralize lethal snake venom toxins

De novo designed proteins neutralize lethal snake venom toxins

Multiplex lateral flow assay development for snake venom detection in biological matrices

A review of antibody, aptamer, and nanomaterials synergistic systems for an amplified electrochemical signal

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