Nanoparticle-siRNA Conjugates

Nanoparticle-siRNA conjugates have generated a paradigm shift and represent the gateway to an entirely new frontier in the landscape of RNA therapeutics, with cancer on the frontline due to the adjacent transformative potential of the therapeutic modality. The major hurdles of siRNA therapeutics are the stability and in vivo effective delivery of siRNA. Significant progress in nanotechnology has enabled the development of optimized siRNA delivery platforms. Leveraging on RNA interference (RNAi), nanoparticle-mediated siRNA conjugates provide a nanoscale platform for inducible gene silencing with exquisite spatiotemporal control over disease-endorsed cascades at a molecular scale. In our role as a leader in biotechnology and pharmaceutical research, BOC Sciences understand the significance of nanoparticle-siRNA conjugates in the development of RNA therapy and commit to supplying clients across the globe with an earnest service.

Nanoparticle-siRNA Conjugates

In this respect, nanoparticle-siRNA conjugates may offer an entirely new dimension in the field of targeted drug delivery, particularly in cancer therapy. The siRNAs, small RNA molecules that can silence specific genes, represent a very attractive new class of genes that can interfere in a specific pathway associated with tumorigenesis. Although, the development of siRNA therapeutics has been hampered by major limitations : poor stability, rapid degradation in vivo and inefficient tissue-target delivery. That is where nanoparticles, convenient vehicles that can encapsulate and secure siRNA molecules, and offer their precise delivery to cancer cells, come into play. This is actually a goal of conjugating siRNA with nanoparticles, to bypass the weaknesses of naked siRNA by conjugating it with nanoparticles and maximize its therapeutic utility. These conjugates provide a number of advantages, which include increased stability, extended half-life in the circulation and increased cell penetration, leading to enhanced RNAi gene silencing activity of siRNAs.

Figure 1. Scheme showing the different types of nanoparticles used in drug delivery for the treatment of the various types of cancers. (A, Rituparna.; et al, 2017)

BOC Sciences' Nanoparticle siRNA Delivery Solution

With considerable experience in the preparation and characterization of nanoparticle-siRNA conjugates, BOC Sciences can provide a full set of customized services for your unique researches. Our scientists have extensive experience with innovative technologies and approaches and expertly design, synthesize and optimize nanoparticle formulations to enable effective delivery of siRNA. Moreover, the versatile nanoparticle-siRNA conjugate services are customized to meet the unique challenges and goals. From targeted tumor type delivery to siRNA loading efficiency, to prognosis in preclinical models and much more, BOC Sciences provides specialized solutions to help expedite our clients' research and development programs.

Custom siRNA Synthesis

BOC Sciences caters for your exclusive demands, providing custom-tailored siRNA synthesis to researchers, drug development, and preclinical applications. We also provide a full range of nucleic acid synthesis services, including siRNA, for loading into nanoparticles.

Nanoparticles Choosing

BOC Sciences offers a selection of organic and inorganic nanoparticle types to choose from.

* For more custom nanoparticle types, please feel free to contact us.

Formulation Design

Working closely with our clients, we design nanoparticle formulations engineered for optimal siRNA encapsulation, stability, and delivery to the desired target. By screening nanoparticle materials and fabrication methods systematically, we can find our way through the space of nanoparticle properties and formulations to one that is optimal for each therapeutic. Each conjugate has unique requirements for siRNA sequence and modification, nanoparticle size, charge, and chemical modification, depending on the application. For nanoparticle-siRNA conjugates to succeed, extensive tuning of nanoparticle properties is necessary to guarantee effective siRNA penetration.

Size & Shape

Research has shown that the size and the shape of nanoparticles determine cellular uptake and biodistribution. BOC Sciences uses the information to design nanoparticles at sizes optimal for improved tumor penetration and cellular internalization. We are aiming to design nanoparticles with specific particle sizes and shapes, which will allow us to further enhance their therapeutic potential and to decrease off-target toxicity.

Surface Charge

Nanoparticle surface charge dictates their ability to interact with biological membranes and modes of cellular uptake. To solve these problems, BOC Sciences finely tune the surface charge of nanoparticles to facilitate their intracellular delivery with minimal cytotoxicity and immunogenicity. By proper choice of surface coatings and functional groups, we attempt to provide nanoparticles with increased biocompatibility and target selectivity for such use.

Hydrophobicity

Hydrophobicity is paramount for many nanoparticle stability and membrane interactions. The hydrophobic nature of the nanoparticles is also exploitable by BOC Sciences to help in packaging and cellular delivery of siRNAs. Herein, we developed hydrophobic functionalized nanoparticle formulations that increase the stability of nanoparticles in physiological milieu and enhance their passage through biological barriers to target delivery of siRNA.

Characterization and Validation

BOC Sciences has developed a multidisciplinary methodology for the characterization of nanoparticle physicochemical properties, in vitro cell-based assays, and in vivo efficacy studies. Our work on thoroughly assessing the biophysical properties and biological behavior of nanoparticle-siRNA conjugates will provide safety, efficacy, and regulatory compliance of these conjugates at the preclinical level.

Why Choose BOC Sciences?

As a leader in drug delivery, BOC Sciences is your reliable partner for the development of nanoparticle-siRNA conjugates, providing expertise, experience and innovation unmatched elsewhere. That is why we are becoming the obvious choice for biopharma companies, academic institutions, and research organizations around the world that demand the best in excellence, scientific integrity, and customer satisfaction.

• Using our unique expertise in bioconjugation chemistry, we ensure the production of high-quality conjugates.
• High-quality, well-defined conjugates.
• Flexible service options.
• Experience and competence of a dedicated team.

Case Study

Case Study 1. Maximizing Therapeutic Potential through Co-Delivery of siRNA and mRNA

Figure 2. Schematic diagram of lipid nanoparticles co-delivering mRNA and siRNA. (Ball, R.L.; et al, 2018)

As compared to the above case, this focuses on modulating gene expression for better treatment of diseases. Hence, researchers investigated the co-formulation of siRNA along with mRNA in a single LNP formulation. A unique formulation of an ionizable lipidoid, cholesterol, DSPC, DOPE, and PEG-lipid was created just to handle different molecular traits in the case of mRNA / siRNA. Interestingly, co-formulated LNPs exhibited an improved efficacy in vitro and in vivo. Consequently, co-delivery of siRNA and mRNA to the same cell in LNP is beneficial to silencing a gene and expression of a gene compared to LNP encapsulating either RNA solely. Low dose siRNAs of 0.03 mg/kg increased silencing of the Factor VII gene from 44% to 87%, and delivery efficiency of mRNA was markedly increased, inducing a threefold higher luciferase protein expression compared to mRNA LNPs. To understand the broader utility of these co-formulation benefits, researchers considered whether the benefits could be extended to LNPs encapsulating a single RNA type for diverse gene therapy needs. Replacing the helper RNA with the addition of the negatively charged polymer polystyrenesulfonate (PSS) retained therapeutic effect at reduced RNA dosage. Together, the co-delivery of siRNA and mRNA in LNPs demonstrates significant potential as a strategy to improve the efficacy of therapeutics in diseases characterized by aberrant gene expression. Additionally, the incorporation of a negatively charged "helper polymer" may represent an attractive strategy to improve LNP potency in LNPs containing a single RNA species. The findings highlight the possibility of designing better RNA-based therapeutics against numerous diseases.

FAQ

1. What are lipid nanoparticles used for?

Lipid nanoparticles are applied for different purposes. The major use is seen as drug delivery systems, helping deliver drugs to certain locations in the body. Lipid Nanoparticles are also used in various areas like gene transfection, gene therapy, and delivery for vaccines, etc. These are tunable and demonstrate promise across several aspects of the medical and biological sciences.

2. What are LNPs for siRNA delivery?

Lipid nanoparticles (LNPs) are used to encapsulate and Delivery small interfering RNAs (siRNAs) to target cells. These siRNAs are then further modified and formulated in a delivery system that has properties to protect the siRNA from degradation in the bloodstream and promote the siRNA to enter into the target cells. Upon entry into the cells, the LNPs free the siRNA for it to target and silence specific genes by obstructing their expression. This technology is anticipated to treat a variety of diseases by inhibiting the harmful genes in the molecular level.

3. What are nanoparticles for siRNA?

Nanoparticles intended to serve as siRNA delivery systems are designed and engineered structures to readily deliver tiny small interfering RNA (siRNA) molecules to the inside of target cells. Lipids, polymers and inorganic (e.g. gold, silica) materials can be used to make these nanoparticles. They package siRNA, shielding it from enzymatic breakdown and helping it to enter cells. These nanoparticles then release the siRNA inside the cells, where they go about exerting their gene silencing effect by disruption the expression of certain target genes. The technology could also have therapeutic applications, such as treating inherited genes, that play a role in disease.

4. What are gold nanoparticle conjugates?

Hybrid structures of gold nanoparticles conjugated (or chemically linked) to other molecules such as antibodies, peptides, DNA, RNA or small molecules, are known as gold nanoparticle conjugates. This conjugate takes advantages of unique properties of gold nanoparticles including small size, biocompatibility, and ease of functionalization, as well as the specific binding capabilities of the molecules attached. Consequently,this mimics have found many applications in the fields of biomedical research, diagnostics and therapeutics.

5. What is small molecule siRNA conjugate?

The small molecule siRNA conjugates is a compound wherein to a small interfering RNA (siRNA) is chemically attached a small molecule. The gene-silencing properties of siRNA are combined with the targeting or other functional properties of a small molecule to form this conjugate. The siRNA is one that is delivered, stabilized, targeted, or modulated for a specific therapy or research need.

6. What is a lipid conjugate siRNA?

A lipid conjugate siRNA is an siRNA molecule that has been chemically linked to a lipid moiety. The attachment allows the siRNA to associate with lipid-based carriers to deliver it into cells, improving the effecacy and specificity of gene silencing in therapeutic and research applications.

References

1. Acharya, R.; et al. siRNA-Nanoparticle Conjugate in Gene Silencing: A Future Cure to Deadly Diseases? Materials Science and Engineering: C. 2017, 76: 1378-1400.
2. Ball, R.L.; et al. Lipid Nanoparticle Formulations for Enhanced Co-delivery of siRNA and mRNA. Nano Letter. 2018, 18(6): 3814-3822.

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