Jyoti Mathur

. Here we developed a clinical-grade approach based on CRISPR-Cas9 non-viral precision genome-editing to simultaneously knockout the two endogenous TCR genes TRAC (which encodes TCRα) and TRBC (which encodes TCRβ). We also inserted into the TRAC locus two chains of a neoantigen-specific TCR (neoTCR) isolated from circulating T cells of patients. The neoTCRs were isolated using a personalized library of soluble predicted neoantigen-HLA capture reagents. Sixteen patients with different refractory solid cancers received up to three distinct neoTCR transgenic cell products. Each product expressed a patient-specific neoTCR and was administered in a cell-dose-escalation, first-in-human phase I clinical trial ( NCT03970382 ). One patient had grade 1 cytokine release syndrome and one patient had grade 3 encephalitis. All participants had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease and the other eleven had disease progression as the best response on the therapy. neoTCR transgenic T cells were detected in tumour biopsy samples after infusion at frequencies higher than the native TCRs before infusion. This study demonstrates the feasibility of isolating and cloning multiple TCRs that recognize mutational neoantigens. Moreover, simultaneous knockout of the endogenous TCR and knock-in of neoTCRs using single-step, non-viral precision genome-editing are achieved. The manufacture of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene-edited neoTCR T cell products and the ability of the transgenic T cells to traffic to the tumours of patients are also demonstrated.

Agriculture crops encounter several biotic and abiotic stresses, including pests, diseases, nutritional deficits, and climate change, which necessitate the development of new agricultural technologies. By developing nano-based fertilizers, insecticides and herbicides, and early disease diagnostics, nanotechnology may help to increase agricultural crop quality and production. The application of silica nanoparticles (SiNPs) may be the solution for increasing the yield to combat the agriculture crisis in the near future. SiNPs have unique physiological properties, such as large surface area, aggregation, reactivity, penetrating ability, size, and structure, which enable them to penetrate plants and regulate their metabolic processes. Pesticide delivery, enhanced nutrition supply, disease management, and higher photosynthetic efficiency and germination rate are all attributed to SiNPs deposition on plant tissue surfaces. SiNPs have been demonstrated to be non-toxic in nature, making them suitable for usage in agriculture. In this regard, the current work provides the most important and contemporary applications of SiNPs in agriculture as well as biogenic and non-biogenic synthetic techniques. As a result, this review summarizes the literature on SiNPs and explores the use of SiNPs in a variety of agricultural disciplines.

Nanotechnology is the promising field with its wide applications in biotechnology, pharmaceutical science, drug targeting, nano-medicine and other research areas. This review highlights the positive and negative impact of nanoparticles on plants and its wide applications in agricultural sciences. Effect of NPs in terms of seed germination, growth promotion and enhancement of metabolic rate has been evaluated by several scientific researches. However, NPs also exert their negative effects such as suppression of plant growth, inhibition of chlorophyll synthesis, photosynthetic efficiency etc. Effects of NPs can be either positive or negative it depending upon the plant species and type of nanoparticles used & its concentration. Modern nano-biotechnological tools have a great potential to increase food quality, global food production, plant protection, detection of plant and animal diseases, monitoring of plant growth nano-fertilizers, nano-pesticide, nano-herbicides and nano-fungicides.

Horticultural and agricultural crops are ruined by numerous fungi, resulting in economic losses and health risks to consumers due to the toxins that fungi produce. Plant resistance has arisen as a result of the uncontrolled use of synthetic chemicals, necessitating the use of greater quantities, resulting in an increase in toxicity in food stuffs. Plant metabolites seem to be one of the best alternatives because they have a lower environmental impact and pose less risk to consumers than synthetic fungicides. The objective of this study is to determine the in vivo and in vitro fungicidal effectiveness of the PKM-2 variety of M. oleifera leaf extract (PKM-2 MOLE) as a fungicide against Fusarium oxysporum, the etiology of wilting in wheat seedlings. PKM-2 MOLE suppressed fungal growth in vitro. There was a significant decrease in illness incidence (78.1%, 69.4%, and 54.1%) and severity (72.2%, 62.1%, and 47.2%) after treatment with PKM-2 MOLE at doses varying from 250 to 1000 mg/kg. Various quantities of PKM-2 MOLE led to an increase in photosynthetic activity, polyphenol content, and antioxidant properties. Plants treated with PKM-2 MOLE produced more antioxidant and defense enzymes, including superoxide dismutase (SOD), peroxidase (POX), polyphenol oxidase (PPO), and phenylalanine ammonia-lyase (PAL). The activities of β-1, 3-glucanase, and chitinase were measured in control and diseased wheat seedlings grown at 10, 20, and 30 days. Plants infected with pathogens were shown to have more activity than control plants. Overall, our results revealed that PKM-2 MOLE is a great alternative for biological destruction of fungal infections, thus reducing dependence on synthetic fungicides.