Strategies to Accelerate Genomic Medicine Development


September 20, 2022

Strategies to Fast-Track Genomic Medicine Development   

 Fast-Track Genomic Medicine Drug Development

Figure 1.Fast-Track Genomic Medicine Drug Development

 

COVID vaccine development has proven that genomic medicines have the potential for faster drug development. Along with potential therapies across screening, prevention, and treatment options, genomic medicines can target the disease-causing gene mutations, offering a more accurate diagnosis and potentially tailored treatments. Unfortunately, many potential drugs remain in research and clinical stages as one of the significant challenges in implementing genomic medicines is the difficulty in establishing strategies to efficiently test the clinical validity of drug candidates.  

 

The first step toward any new drug development is the identification of a biological target (e.g., a receptor, protein, gene, etc.) that is dysfunctional in patients with the disease. The next step is the discovery and development of entirely new medicines with a different mode of action or iterative improvements on current medications in terms of potency, safety, tolerability, or convenience. On average, it takes over 12 years1 and often much longer from discovery to commercialization of new medicine. Nucleic acid therapeutics that use Ribonucleic Acid-Lipid Nanoparticle (RNA-LNP) technology has emerged as a promising approach for creating safe, targeted treatments that act on specific cells in a much shorter time, offering endless possibilities for new therapies.  

 

The ability of mRNA-LNPs to induce the expression of nearly any protein makes them invaluable in personalized medicine, gene-editing, and immuno-oncology applications. However, the biggest hurdle in developing nanomedicine is the difficulty in delivering these therapeutics to their target cells. Nucleic acids require drug delivery systems to facilitate their intracellular delivery into target cells.  

Drug development stages

Figure 1. Five key stages in the development of LNP-based drug products 

 

LNPs have been widely studied as a non-viral delivery vehicle for nucleic acids, especially after the approval of the Onpattro® (Patisiran) and COVID-19 vaccines. Lipid nanoparticles consist of ionizable lipids, helper lipids, cholesterol, and PEG lipids, each having a specific role. The ratio and chemical properties of each component affect the LNP efficiency and ionizable lipids  are one of the key strategic components that can greatly influence the LNP properties and efficiency. Optimizing these lipids can help overcome drug-delivery challenges, unlocking potential new genomic medicines in a shorter time.

 

Scalable NxGen™ Technology  

Microfluidic mixing is an established go-to technology for producing RNA lipid nanoparticles. However, the mixing mechanism, temperature, pH, nanoparticle composition, and shear forces affect the self-assembly process during LNP production. Further processing steps are labor intensive and can result in poor batch-to-batch reproducibility, making scaling difficult. This can result in low nanoparticle efficacy, impact particle biodistribution, and inconsistent results. Consequently, this makes it difficult to establish trends or apply rational design principles and ultimately leading to delay in drug development. To overcomes these challenges, it is advantageous to use a technology that can be easily scaled up to develop a consistent potent formulation. NxGen™ is the only technology that can scale from lab scale to commercial batch sizes with the same mixer design with low hold-up volumes. It uses precisely controlled mixing to generate optimal particles through a single mixer enabling the reproducible scale up of mRNA lipid nanoparticles and other complex nanomedicine formulations. The proprietary NxGen™ technology at the heart of Precision NanoSystems’ NanoAssemblr® platforms is designed for genomic medicine development. Therefore, investing in such cutting-edge technology advances successful drug development.

Accelerate Pre-Clinical Programs  

Pre-clinical program objectives are to deliver one or more clinical candidate formulations with sufficient evidence of biological activity at a disease-relevant target while demonstrating safety and potency. To identify lead candidates for nucleic acid delivery to specific cell types, LNP formulations are typically screened using in vitro assays to identify top candidates that are further investigated in animal models. The raw materials for running these assays are limited and costly, thereby requiring exceptional proficiency to combine the nucleic acid and LNP components in the correct ratio and scalable manner to avoid problems that might occur at the clinical scale.  

This is a critical stage in the drug development process and choosing the right technology and expertise at the early stages makes a huge difference in saving time and cost. Thus, access to advanced instruments fit for discovery at an early stage is a remarkable step forward. The NanoAssemblr Spark™ that works on NxGen™ technology considerably accelerates screening workflows for identifying novel LNPs for biological applications. It overcomes the challenges of traditional techniques for the controlled and reproducible manufacturing of LNPs at volumes from 50 to 250 µL, encapsulating several µg of nucleic acid. Formulation creation takes less than 10 seconds, and the resulting LNPs can be diluted and applied immediately to cells in culture.  

Vaccines, gene therapy and cell therapy demand different characteristics from lipid nanoparticles; eliciting appropriate immunogenicity or eluding other indications are important to consider when formulating mRNA medicines. Therefore, it is significant to also focus on testing and optimizing to make promising formulations. To save time and cost of raw material in developing these formulations, Precision NanoSystems offers a lipid nanoparticle portfolio  and LNP formulations designed for specific applications, including biopharma services to help in selecting appropriate lipids for custom applications.  

Precision NanoSystems also offers a GenVoy-ILM™ Delivery Platform comprising off-the-shelf RUO reagents that can quickly and easily prepare RNA-LNP for discovery and proof-of-concept studies with a clear path to the clinic for later development. These easy-to-use kits enable any researcher to become a genomic medicine developer as they offer lipids for broad and targeted applications without requiring in-depth knowledge of LNP formulation or optimization. This allows researchers to save time while validating target payloads and lower the risk of developing a bespoke lipid nanoparticle formulation, thereby accelerating pre-clinical programs for genomic medicine development.

Fast-track Clinical Drug Development  

 Fast-track drug development

Figure 2. Fast-track drug development

 

For most emerging and re-evolving devastating infectious diseases, the main obstacle is developing medicine in a short timeframe. The medical promise of mRNA-LNP technology has been realized with the full approval of rapid-response mRNA vaccines against COVID-19. Moreover, it highlighted the importance of vaccine technologies capable of rapid deployment for human trials. Therefore, nucleic acid therapeutics can fill the gap between a disease epidemic and a desperately needed vaccine.

For fast-track drug development, it is important to prove the success of the lead candidate quickly to move towards the clinical phases. Precision NanoSystems enables researchers to develop in-house expertise and processes through extensive support and education by not only helping in selecting appropriate formulations but through its scalable LNP manufacturing NanoAssemblr® instruments with NxGen™ technology that span pre-clinical and clinical batch sizes. Furthermore, the technology opens avenues for many other drug candidates in the future across different applications. The applications, lipids, and payloads can vary with the target disease; however, the same instruments, lipid library, off-shelf reagent kits, and the proprietary NxGen™ technology can be used for developing new drug products. It is noteworthy that Precision NanoSystems is building its own RNA medicine, projected to complete by early 2023, the project is funded by the Canadian government focuses on expanding epidemic and pandemic preparedness capacity.

Sirnaomics QuoteSirnaomics, a clinical-stage RNA therapeutics biopharmaceutical company, used a bench scale NanoAssemblr® instrument to conduct proof of concept studies in 2018 and successfully ran GMP batches by April 2020.  These timelines prove that faster drug development times are achievable by using advanced NanoAssemblr® instruments.

Precision NanoSystems instruments provide an estimated 4-month acceleration for rapid composition and formulation, as well as an 8-month acceleration with faster process optimization and scale up with the right lead formulations for GMP manufacturing.

 

Establish Strategic Partnerships for Accelerated Drug Development 

Accelerate drug development of genomic medicines through trusted partnership

Figure 3. Accelerate drug development of genomic medicines through trusted partnership

 

Certainly, developing genomic medicines with LNP technology is faster and safer, however it is only possible with the right instruments and expertise. Precision NanoSystems has a trusted reputation for its instruments cited in >500[KR9]  respected scientific publications. It offers end-to-end services for drug development, including instrumentation, lipids, and expertise across all stages. One of Precision NanoSystems’ successful global academic partnerships with Imperial College, London demonstrated accelerated development timelines in a study conducted for developing the COVID-19 vaccine and HA against influenza. With access to the Precision NanoSystems’ lipid library, the researchers were able to quickly choose application-specific LNP compositions to begin phase 1 and 2 clinical trials.

Precision NanoSystems provides exceptional lipid formulations and nanoparticle development expertise for success in numerous applications while reducing the risk of failure and delays. The biopharmaceutical services team has broad technical knowledge and experience in payload design and lipid-based delivery systems- lipid nanoparticle and lipopolymer formulations across a wide range of disease applications. Furthermore, partnering with established LNP leaders also gives leverage in optimization and technology transfer of manufacturing processes for cGMP production and assistance with CMC regulatory submissions.

Partner with a proven LNP technology leader and trusted biopharma team to accelerate end-to-end genomic medicine development from discovery to the clinic.

 

References:

1. Mohs RC, Greig NH. Drug discovery and development: Role of basic biological research. Alzheimers Dement (N Y). 2017 Nov 11;3(4):651-657. doi: 10.1016/j.trci.2017.10.005. PMID: 29255791; PMCID: PMC5725284.

 

Advanced Search

close
  • Publications
  • Application Notes
  • Posters
  • Workshops
  • Videos & Webinars
  • Articles
Search

Browse by Category

  • Application
    • Diagnostic and Imaging
    • Genetic Medicine
    • Hematology
    • Metabolic Disorders
    • Neuroscience
    • Oncology
    • Skeletal Disorders
    • Targeted Drug Delivery
    • Vaccines
    • Other Applications
    • Cell therapy
  • Formulation
    • Liposomes
    • Nucleic Acid Lipid Nanoparticles
    • Polymeric Nanoparticles
    • Other Formulations
  • Payload
    • DNA
    • microRNA
    • mRNA
    • siRNA
    • Small Molecule Drugs
    • Other Payloads


related content

Article

Nanomedicine offers promising therapeutic solutions for cell and gene therapies, autoimmune diseases, oncology, rare inherited diseases and more. Some new avenues to explore include early disease detection or molecularly tailored treatments for patients who have complex diseases ...
Read More


Article

The production of RNA lipid nanoparticles (LNPs) such as those used in COVID-19 vaccines involves mixing RNA in an aqueous buffer with lipids dissolved in ethanol to trigger the self-assembly of LNPs. The mixing conditions of the RNA and lipids are crucial to drug product quality...
Read More