Clinical Development

Delivery Systems for

Clinical Development


What we Do

We are developing novel delivery systems to effectively deliver nucleic acid therapeutics in a clinical setting. Scaled-up synthesis procedures have been implemented to produce our transfection reagents in large quantities. Efforts to produce GMP-grade materials are ongoing. We are committed to undertaking the required safety and toxicological studies to facilitate clinical testing of our delivery systems.

Our R&D Focus

One area of focus for RJH Biosciences is to implement RNA interference (RNAi) via delivery of short interfering RNA (siRNA). Our initial therapeutic application is blood cancers, while recognizing that the RNAi activity can be implemented in the treatment of a large range of human cancers and other diseases. Another focus is direct administration of plasmid DNA (pDNA) to express therapeutic proteins in situ, with applications in immunotherapy.
The R&D activity is at the preclinical stage and we are committed to undertaking the initial development of our therapeutic agents in select human disorders. We actively seek partners in blood cancer and immune cell based therapeutic areas for clinical collaborations. We have been adopting our delivery systems for treatment of patient-derived cells as well as preclinical animal models. Reach out to us if you desire to use our reagents in particular disease models.

Why study blood cancers and immunotherapies with nucleic acid therapeutics?

There are three types of blood cancers: Leukemia, lymphoma, and myeloma. Leukemia is characterized by highly proliferating, abnormal white blood cells [1]. Lymphoma and myeloma are respectively cancers of the lymphatic system and plasma cells which greatly effect the immune system [2,3]. These three cancers are difficult to treat and the current treatments are limited in efficacy, especially at the end stage of the disease.
The use of nucleic acid-based therapeutics can eradicate these cancers in two primary ways, with RNAi technology and cell-based immunotherapy. The use of RNAi is being increasingly explored in the treatment of the blood cancers. Polynucleotides such as siRNA has aided the downregulation of oncogenes and can be designed to support specific abnormalities in individual patients, making it a ‘personal’ strategy with a universal technological design [4]. Due to siRNA’s potential in blood cancer therapies, we are currently focusing on siRNA therapeutics in our R&D projects, targeting disease-driving oncogenes and inducing apoptosis in the malignant cells.
Another strategy that is being explored for treating blood cancers is the use of immunotherapy. Immunotherapeutic strategies include the use of antibodies, stem cell transplants, cytokines, small molecules among others [5]. However, a more recent approach is genetic therapy by using engineered cells, also known as Cell Transfer Therapy. This method works by taking patients’ own immune cells such as but not limited to T-cells, B-cells, and NK cells. The immune cells genome is engineered to support various therapeutic strategies that may involve neoantigen expression and presentation on immune cell surface, and then are reintroduced into the host [5]. The modified cells are ultimately designed to target and remove the malignant cells. This strategy is highly advantageous as T-cells can ‘seek’ and destroy the malignant cells in the blood system. While this approach has been promising in blood cancers, it can be also used in other solid cancers. As the foundation of immunotherapy relies on nucleic acid introduction into patient cells, efficient delivery of nucleic acids is imperative for success. Our transfection reagents offer the best in class vehicles to undertake such a delivery.
Nanomedicine based on nucleic acid therapeutics is a large component to personalized cancer therapies and immunotherapies. The RJH Biosciences strives to provide quality transfection reagents, whether it involves the delivery of our own nucleic acid candidates or our customers’.

References:

  1. Jean, C. and Dick, J. (2005) Cancer stem cells: lessons from leukemia. Trends in cell biology. 15, 494-501.
  2. Woods, N. et al. (2006) Therapueti gene causing lymphoma. Nature. 440, 1123.
  3. Mahindra, A. et al. (2012) Latest advances and current challenges in the treatment of multiple myeloma. Nature Reviews Clinical Oncology. 9, 135-143.
  4. Uludağ, H. et al. (2016) Current attempts to implement siRNA-based RNAi in leukemia models. Drug Discovery Today. 21, 1412-1420.
  5. Zou, W. (2006) Regulatory T cells, tumour immunity and immunotherapy. Nature Reviews Immunology. 6, 295-307.
For disorders beyond the focus of RJH Biosciences, we are open to working with pharmaceutical and biotechnology companies in other clinical indications. Our delivery systems were shown to be effective for a range of nucleic acids and we are confident that we can implement nucleic acid therapies in a range of diseases.

Relevant Research

The following publications provide a glimpse of our scientific studies with patient cells and animal models.
  • Valencia-Serna et al. siRNA-mediated BCR-ABL silencing in primary chronic myeloid leukemia cells with lipopolymers. J. Controlled Release (2019) 310: 141-154.
  • Thapa et al. Breathing new life into TRAIL for breast cancer therapy: co-delivery of pTRAIL and complementary siRNAs for breast cancer therapy using lipopolymers. Human Gene Therapy (2019) 30: 1531-1546
  • Valencia-Serna et al. siRNA/Polymer nanoparticles to arrest growth of chronic myeloid leukemia cells in vitro and in vivo. European J. Pharmaceutics and Biopharmaceutics (2018) 130: 66-70.
  • Landry et al. Targeting CXCR4/SDF-1 axis by lipopolymer complexes of siRNA in acute myeloid leukemia. J. Controlled Release (2016) 224: 8-21.
  • Aliabadi et al. Effect of siRNA pre-exposure on subsequent response to siRNA therapy. Pharm. Res. (2015) 32: 3813-3826.
  • Gul-Uludag et al. Nanoparticle-mediated silencing of CD44 receptor in CD34+ acute myeloid leukemia blasts. Leukemia Research (2014) 38: 1299–1308.