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Murine Leukaemia Virus-Like Particles (MLVLPs)

Background MLVLPs Services Highlights FAQs Published Data

Background

Creative Biolabs offers top-tier MLVLP production and RNA delivery services, including custom aptamer design, ensuring precise and efficient gene delivery with high specificity.

  • Overview of MLVLPs

In recent years, retroviral-like particles (VLPs) have gained attention as promising tools for various applications in molecular biology and biotechnology due to their unique properties. Unlike traditional retroviral vectors, VLPs are devoid of viral genetic material, thereby minimizing the risk of genomic integration and unwanted genetic alterations in host cells. One notable example of VLPs is the Murine Leukemia Virus-like particles (MLVLPs), which have emerged as efficient carriers for delivering mRNAs into target cells. MLVLPs offer a safe and effective alternative for gene delivery, particularly in applications where transient expression of exogenous genes is desired without the risk of genomic integration. A key strategy employed in utilizing MLVLPs for RNA delivery involves the incorporation of specific RNA aptamers and their corresponding aptamer-binding proteins (ABPs) into the particle structure. RNA aptamers are brief, single-stranded RNA molecules characterized by their high affinity and specificity towards target molecules. These aptamers can be engineered to bind to various proteins with exceptional specificity, making them valuable tools for targeted delivery applications. Creative Biolabs provides several pairs of RNA aptamers and ABPs, which have been successfully employed in MLVLP-mediated RNA delivery systems. For example:

  • MS2 RNA aptamer/MS2 coat protein (MCP)
  • PP7 RNA aptamer/PP7 coat protein (PCP)
  • Com RNA aptamer/Com protein
  • BoxB RNA aptamer/λ N22 peptide

Each aptamer is specifically designed to bind with high affinity to its corresponding ABP, facilitating the efficient encapsulation of RNA cargo within the MLVLP structure. This selective binding ensures precise delivery of the desired RNA payload to target cells or tissues, enhancing the efficacy and specificity of gene delivery applications.

  • Application of MLVLPs

In general, incorporating RNA aptamers and ABPs into MLVLP-based delivery systems is a potent approach for achieving precise and efficient RNA delivery. Figure 1 illustrates the utilization of the MS2 and MCP interaction for the MLVLP-mediated delivery of Cas9 mRNA. To achieve this, the nucleocapsid protein within the Gag protein was substituted with 2 copies of MCP, and 2 copies of the MS2 aptamer were introduced into the 3' UTR of Cas9 mRNA at various positions along with sgRNA. This strategy aimed to utilize MS2/MCP interactions to effectively entrap Cas9 mRNA and sgRNA within the VLPs. These MLVLPs effectively induced DNA mutations across a variety of murine and human cell lines, encompassing human T cells, primary human fibroblasts, and CD34+ stem and progenitor cells derived from cord blood.

Fig.1 Simplified structure diagram of MLVLPs. (Knopp, et al,2018)Fig.1 The MS2 and MCP interaction for MLVLP-mediated delivery of Cas9 mRNA.1

Murine Leukaemia Virus-Like Particles Services

Creative Biolabs is dedicated to providing top-tier MLVLPs services globally. Our services encompass MLVLPs production, purification, and titer titration, alongside comprehensive offerings for aptamer design and synthesis. Reach out to us for further details, and we assure you of our unparalleled service quality.

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Highlights

  • Safe Gene Delivery: MLVLPs enable gene delivery without the risk of genomic integration.
  • Custom Aptamer Incorporation: They use RNA aptamers for targeted delivery.
  • Versatile Applications: Effective in multiple cell types including human T cells and stem cells.
  • Comprehensive Services: Includes production, purification, and titration.
  • Global Availability: Creative Biolabs provides these services worldwide.

FAQs

Q: What are murine leukaemia virus-like particles (MLVLPs)?

A: MLVLPs are retroviral-like particles without viral genetic material, used for safe and efficient RNA delivery in molecular biology.

Q: What makes MLVLPs safer than traditional retroviral vectors?

A: MLVLP is safer than traditional retroviral vectors because it is replication-deficient, reducing the risk of insertional mutagenesis and limiting unintended gene integration, making it a more controlled option for gene therapy.

Q: What applications are MLVLPs suitable for?

A: MLVLP is suitable for gene therapy, vaccine development, and functional genomics studies, offering efficient gene delivery with reduced safety risks, particularly in applications requiring stable gene expression without replication.

Q: How do MLVLPs achieve targeted RNA delivery?

A: MLVLP achieves targeted RNA delivery by incorporating specific ligands or surface modifications on the viral particles, enabling precise binding and entry into target cells, ensuring efficient and localized gene expression.

Q: What services does Creative Biolabs provide for MLVLPs?

A: Services include MLVLP production, purification, titer titration, and aptamer design and synthesis.

Published Data

In the study, Murine Leukemia Virus-Like Particles (MLV-VLPs) were engineered to serve as a biological delivery system for therapeutic proteins. These particles were designed to deliver bioactive proteins, such as nuclear transcription factors and toxic proteins, into target cells without transferring viral RNA. The experiments demonstrated that MLV-VLPs could successfully deliver and activate nuclear transcription factors within cells by incorporating nuclear export signals. Additionally, when delivering the bacterial toxin MazF, which induces cell death, the system proved effective, with the producer cells being protected by co-expressing the anti-toxin MazE. This approach highlighted the potential of MLV-VLPs as a versatile platform for delivering therapeutic proteins to modulate cellular processes, offering a promising method for therapeutic interventions.

Evaluation results of the biological delivery function of MLV-VLPs.

Fig.2 Biological activity of VLPs containing bacterial MazEF toxin-antitoxin cassette.2

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References

  1. Knopp, Yvonne, et al. "Transient retrovirus-based CRISPR/Cas9 all-in-one particles for efficient, targeted gene knockout." Molecular Therapy-Nucleic Acids13 (2018): 256-274.
  2. Wu, Dai-Tze, and Monica J. Roth. "MLV based viral-like-particles for delivery of toxic proteins and nuclear transcription factors." Biomaterials 35.29 (2014): 8416-8426.
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