Selective sodium iodide symporter NIS gene therapy of glioblastoma mediated by EGFR-targeted lipopolyplexes

Selective sodium iodide symporter NIS gene therapy of glioblastoma mediated by EGFR-targeted lipopolyplexes

These ASOs were modified using the ‘Gapmer’ strategy and 2′-O-methyl modifications at 5′ and 3′ ends. To enhance the targeting and delivery, cancer cell-specific lipid nanoparticles (conjugated with transferrin receptor-targeting top websites for buying anabolic steroids T7 peptide) were synthesized with these modified ASOs [224]. The ASO co-loaded nanoparticles exhibited enhanced colloidal stability, high encapsulation with smaller particle size, and higher cellular uptake.

  • These formulations possess PEG at high density on the surface, which decreases the undesired interactions of ASOs with DNA and proteins (protecting from enzymatic degradation) and enhances the chances of antisense overhangs to hybridize with target mRNA, thereby reduce protein expression.
  • Some species release anti-bacterial compounds from their seeds, which can inhibit the inoculant.
  • The number of nodules, which is the most important quality criteria for an inoculant for legumes, was high when the number of surviving bacteria on the seeds was high (Maurice et al. 2001).
  • The analysis of patient blood samples suggested that miRNA-4315 and cytochrome-c levels help define the timeline to add ABT263 to enhance cell death and overcome anti-PD1 resistance [307].

The identification of antisense sequences, short interfering RNAs (siRNAs), microRNAs (miRNAs or miRs), anti-miRs, and mRNA-based platforms holds great promise in preclinical and early clinical evaluation against LC. In the last decade, RNA-based therapies have substantially expanded and tested in clinical trials for multiple malignancies, including LC. This article describes the current understanding of various aspects of RNA-based therapeutics, including modern platforms, modifications, and combinations with chemo-/immunotherapies that have translational potential for LC therapies. Small RNA therapies substantially affect the growth of LC, and thus targeted RNA combination therapies may be used to improve therapeutic response. Several efforts have been made to improve the utilization and formulations of RNA-based cancer therapeutics, such as the use of nanoparticles as a delivery vehicle [158, 251]. Interestingly, the nanoparticles-based delivery systems not only protect the small molecule RNAs from degradation but also facilitate the evaluation of different combinational approaches to develop effective LC therapies.

Dried polymeric carriers

“Carrier” refers to the abiotic substrate (solid, liquid, or gel) that is used in the formulation process. “Formulation” refers to the laboratory or industrial process of unifying the carrier with the bacterial strain. “Inoculant” refers to the final product of formulation containing a carrier and bacterial agent or consortium of microorganisms. “Quality control” refers to the process of measuring defined quality parameters of the inoculant.

  • Hardware developments, navigation and acquisition strategies, and emerging solutions for data processing in innovative applications are considered in this analysis.
  • PVP is a synthetic vinyl polymer that aids survival of Bradyrhizobium japonicum (Singleton et al. 2002).
  • This phenomenon, combined with poor production of bacterial biomass, difficulty sustaining activity in the rhizosphere, and the physiological state of the bacteria at application time, can prevent the buildup of a sufficiently large PGPB population in the rhizosphere.
  • By combining the best of our nearly half century years of blood pressure measurement experience with the capability to apply traditional methods of blood pressure measurement, the ADC AdView™ provides the most reliable and versatile means of capturing blood pressure data.
  • The literature describes many forms of tested inoculants (see below and in Table 1), but commercial inoculants come in only a very few variations.

RNAi is a mechanism used by the cells to downregulate gene expression in genetic abnormalities and infections [38]. Hence, RNAi approaches were explored and adapted as a potential therapeutic strategy for treating different diseases, including cancer [38, 47, 96,97,98]. Two PGPB, Azospirillum brasilense and Pseudomonas fluroescens, immobilized in two types of alginate-bead inoculant (with and without skim-milk supplement) and later dried and stored at ambient temperature for 14 years, were recovered.

Technical aspects of inoculant production

Nitrogen-fixing cyanobacteria are used sporadically as a supplement to chemical nitrogen fertilizers for rice cultivation in India and Bangladesh. Field trials showed that cyanobacterial inoculants solve problems in acid and saline soils, improve their fertility status, and may add 25–35% of the nitrogen for rice cultivation in these soils (Hashem 2001). Local strains of PGPB from Vietnam were added to an unsterile carrier formulated by mixing clay soil, rice husks, sugar, water, and broth culture. These bacterial cultures were mixed in the field immediately before inoculating rice seedlings at the time of transplantation, resulting in increased rice yields (Nguyen et al. 2003). Survival of Azospirillum brasilense in turf used as a carrier of several grasses supported viability of A.

  • Practically, carrier material is packed in thin-walled polyethylene bag and then γ-irradiated.
  • It is also impractical for large-scale application; the large volume of liquids involved, incubation, and refrigeration facilities needed to maintain culture medium that have no formulation make it unlikely to meet economic and commercial needs.
  • Since the discovery of rhizobia in 1886 (Hellriegel 1886, cited in Date 2001) and for about 120 years, Rhizobium inoculants have been commercially produced worldwide, mainly in developed countries (Catroux et al. 2001; Deaker et al. 2004).
  • The polyglutamate-derived brush polymer-based silencing of survivin using si-RNA (PPGS/si-survivin polyplex) combined with cisplatin exhibited synergistic cytotoxic effects on drug-resistant LC cells [297].

Similarly, in SCLC, oblimersen failed to show benefit, either alone or in combination with chemotherapy (Table 1) [285]. The outcome of a phase II clinical trial, evaluating the efficacy of carboplatin and pemetrexed plus either apatorsen, a Hsp27 mRNA targeting ASO, or placebo showed no additional toxicity; however, no improvement was observed in treatment naïve patients with metastatic nonsquamous NSCLC [306]. Another application of alginate inoculants is in tertiary wastewater treatment by microalgae (de-Bashan and Bashan 2010).

Yet, apparently, this formulation suffers from short shelf life, high contamination, and low field performance, but it is still used in experiments (Bharathi et al. 2004; Saravanakumar et al. 2007a, b, 2009). Gum arabic is a complex carbohydrate extracted from acacia and a commonly used adhesive for rhizobia (Deaker et al. 2011). The nickel- and zinc-tolerant PGPB Bradyrhizobium sp., isolated from nodules of green gram promoted growth of this plant in nickel- and zinc-contaminated soils when inoculated with gum arabic in a liquid culture as an adhesive (Wani et al. 2007). This was also done with the inoculant Rhodobacter capsulatus to improve growth of rice (Gamal-Eldin and Elbanna 2011).

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The successful safety and efficacy outcomes of these vaccines are likely to enhance the enthusiasm and trust, and likely to dictate the future course of RNA-based therapeutics in general. Based on recent mRNA-based cancer vaccine studies in melanoma [51] and other infections like COVID-19 mRNA-based vaccine, the developmental route map for the mRNA-based LC vaccines is outlined in Fig. The seminal paper published by Andrew Fire and Craig C. Mello in 1998 suggested the role of double-stranded RNAs in post-transcriptional gene silencing through a mechanism known as RNA interference (RNAi) and revolutionized the field of gene silencing [93]. This study contributed to the understanding of gene silencing and/or expression-related puzzles in fungi and plants and hit out the field by establishing the central role of non-coding RNAs in gene expression. These small/short interfering RNAs (siRNAs) are processed from longer dsRNAs by ribonuclease III and maintain a characteristic structure (with 5′-phosphate/3′-hydroxyl ends) with a 2-nucleotide 3′-overhang on each duplex strand [94, 95]. These studies established that the siRNA molecule induces RNAi in mammalian cells without undesired interferon responses and is now accepted as a simplistic universal biological tool for gene silencing studies.

As the number and the heterogeneity of debated topics are large, the paper is organized according to very specific questions considered most relevant by the authors. While this section is primarily the domain of production facilities for inoculants, these aspects are interlinked with formulation and application of inoculants. They form one chain of events linking research facilities to the industry and the farm; the latter might be agricultural or environmental.

Agricultural uses of plant biostimulants

This curing favors adaptation of rhizobia to the carrier and increase tolerance to drying (Albareda et al. 2008). All this happens because rhizobia are metabolically active and as long as nutrients and favorable environmental conditions prevail, they continue to grow inside the inoculant. When the bacterial population declines from dehydration, the surviving numbers are higher. Using various organic, inorganic, and polymeric formulations, Bacillis subtilis survive at room temperature (~22 °C) for 45 days, but Pseudomonas putida requires refrigeration (~0 °C) and depends on the type of carrier that is used (Amer and Utkhede 2000). Liquid inoculants produced in the field by fermenters and immediately applied are uncommon and only a few exist for turf grass for golf courses and limited hydroponic cultivation. For common agricultural uses, inoculants made of peat or other organic and inorganic materials and a storage period between manufacturing and use, is usually required.

ASOs-dA40/SPG targeting KRAS inhibited KRAS expression in Dectin-1 expressing LC cells and correspondingly decreased cell growth. This ASOs-dA40/SPG complex enhanced the cytotoxic effect of gemcitabine due to the ability of dA40 moiety to directly interact with gemcitabine. Interestingly, after internalization, this interaction dissociates, and gemcitabine is easily released from the complex [214].

It is paramount to get an inoculant to perform well in the type of soil where it is applied. The literature describes many forms of tested inoculants (see below and in Table 1), but commercial inoculants come in only a very few variations. Although some reviews briefly mentioned formulations and practical aspects of inoculants, none of these recent reviews concentrated on that topic; this is the niche selected for this review. Several groups are also developing anti-miR drugs against miR-21, miR-17, miR-155, and miR-29 for cancer, kidney, and other diseases [58, 145,146,147,148]. These miRNAs (especially miR-21) have a diverse role in lung cancer establishment, progression, and metastasis, so these anti-miRs can also be utilized as an effective therapy for lung cancer.

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