Vector systems (gene delivery vehicles) used in manufacturing of Gene Therapy Medicinal Products (GTMPs)

Desired outcome

Design and manufacture of a suitable vector system for gene therapy medicinal product (GTMP) delivery is a crucial step to achieve safe and efficient gene therapy medicinal product.

Initial Problem Description

The initial step in developing Good Manufacturing Practice (GMP)-compliant vector systems for Gene Therapy Medicinal Products (GTMP) involves conducting an extensive literature review. The focus of our research will be on the following aspects:
-Current GMP-Compliant Vector Systems for GTMP (Identify and evaluate existing GMP-compliant vector systems for GTMP, including an analysis of their pros and cons)
-Production of Vector Systems (Explore the production processes of these vector systems, encompassing the necessary equipment for specific manufacturing platforms, quality control testing, and options for large-scale GTMP production. Additionally, estimate the costs associated with establishing a particular manufacturing platform.)
- Future Gene Delivery Vehicles (Investigate emerging gene delivery vehicles and those currently in the research phase to understand the future landscape of vector systems for GTMP.)
- Which vector system would you use for GTMP delivery and how would you design a GMP compliant vector delivery system manufacturing platform?

Given the comprehensive nature of the topic, our research will particularly focus on:
-GMP-Compliant RNA Delivery Systems (50% of the work) (Emphasize the production of GMP-compliant RNA delivery systems, encompassing both viral delivery vehicles and non-viral delivery systems. Pay special attention to the production of lipid nanoparticle-mRNA formulations, assuming that the RNA production platform is already established.)
-Adenoviruses as Gene Delivery Systems (40% of the work) (Explore the production processes and considerations associated with adenoviruses as gene delivery systems.)
-Future Vector Systems in Research Phase (10% of the work) (Investigate and provide insights into the vector systems currently in the research phase for GTMP.)

This structured approach will guide our research efforts and ensure a comprehensive understanding of GMP-compliant vector systems for GTMP delivery.

Context

Key step in gene therapy is efficient and safe gene delivery to the target tissue/cells. Vectors must protect genetic material from degradation, maximize delivery to on-target cells, minimize exposure to off-target cells, ensure scalability and enable highest stability and bioavailability of drug substance.

Connection to cross-cutting areas

Establishment of one universal platform for each vector system and optimization of process development would lead to the identification of more sustainable and resource-efficient methods (reduction in material and reagent consumption). As gene therapy and related technologies advance, it is crucial to consider the social and ethical aspects of their development and implementation. Ensuring equitable access to GTMPs and addressing ethical concerns contributes to the overall sustainability of these technologies.

Input

The most commonly vector system used for RNA delivery is lipid nanoparticle-mRNA formulation, which is also the delivery formulation used in first FDA siRNA approved drug Onpattro and in mRNA-1273 and BNT162b Covid-19 vaccines. Main composition of these lipid nanoparticles is pH sensitive ionizable lipids, which enable higher bioavailability due to more efficient endosomal escape of nanoparticles. Commonly used nanoparticle synthesis method is rapid mixing where lipid components are in ethanol phase and RNA molecules in aqueous phase, but the specific and optimal conditions (pH, flow rate) still must be determined.

Expectations

Conducting a literature review in the field of Good Manufacturing Practice (GMP) compliant production of vector systems (gene delivery vehicles) used in Gene Therapy Medicinal Products (GTMPs), innovative design of the 'ideal' gene delivery vehicle, and determination of the main bottlenecks in GMP-compliant production of gene delivery vehicles.

Desired Team Profile

Motivated students/researchers of natural science (biology, biotechnology, microbiology, pharmacy, biochemistry etc.) with basic knowledge of biotechnology and pharmacy or anyone interested in the field of gene therapy (we will provide missing information and support you during the Challenge solving).

Additional Information

To help the selected team promptly deliver results, one team member of Jafral will be designated for this project on our side so that communication can be quick and efficient through the platform. If any questions arise, an assigned person will guide you while searching for the solution. We are happy to collaborate!

Related Keywords

• Biological Sciences
• Biology / Biotechnology
• Genetic Engineering Technology