Challenges and Opportunities in Live Biotherapeutic Products Development

Live biotherapeutic products (LBPs) have emerged as promising new drugs under the advancement of biotechnology. Currently, some drugs for certain diseases have shown some disadvantages, including inadequate efficacy, hypersensitivity and resistance, side effects caused by long-term use, and high cost. In the face of this situation. LBPs provide a new approach to drug development, with specificity, targeting, and safety advantages providing broad application prospects in a variety of disease types. To further promote the development of LBPs and fully exploit their advantages, the following aspects need to be considered and improved:

1. Single-strain LBPs have a single ingredient and clear efficacy, but they are selected from nature and therefore have a certain degree of randomness in development. The efficacy and strain composition, strain characteristics, and interactions between multiple strains of multi-strain LBPs are closely related. Therefore, the efficacy model and stability evaluation of multi-strain LBPs are more complex than single-strain LBPs. Multi-strain LBPs may have better efficacy than single-strain LBPs, but the efficacy dosage model of single-strain LBPs is more straightforward, making it easier to control the efficacy. Engineered LBPs have unique advantages, such as better targeting, lower dosages, fewer toxic side effects, and most importantly, they can be artificially modified to have specific desired functions, thus having a wider range of applications. As people have a more comprehensive and objective understanding of gene-editing drugs, it is believed that engineered LBPs will become increasingly popular.

2. When treating metabolic diseases caused by an enzyme deficiency, engineered LBPs usually introduce new enzyme genes into its system. Therefore, the specificity and activity of the introduced enzymes should be carefully evaluated to avoid other unexpected metabolic disorders. When constructing engineered bacterial strains, stable and quantifiable bacterial functional biomarkers can be included in the bacterial strain design. These biomarkers can clarify the pharmacokinetics and pharmacodynamics of engineered LBPs, promoting the translation from pre-clinical models to clinical studies.

3. The safety of engineered bacterial therapy is crucial and biological containment strategies, such as using nutrient-deficient or kill-switch engineered bacteria, can be used. Poison gene insertion can also be used in engineered bacterial plasmids to prevent gene displacement. Designing specific protein particles for plasmid replication can also prevent the spread of engineered bacterial DNA to specific bacterial strains. Researchers should also conduct strict safety tests of live biotherapeutic products, including morphological inspection, physiological and biochemical identification, drug sensitivity experiments, and genotoxicity tests.

4. The stability of live biotherapeutic products is essential because LBPs are made of living microorganisms, which means their efficacy may be influenced by multiple factors, including drug dosage, transport and storage conditions, substrate types, packaging technologies, and administration methods. Therefore, further research is needed to clarify the impact of production processes, substrate, and storage conditions on bacterial viability. Besides, dose-response evaluations of LBPs should be conducted under different environmental, dietary, and administration schemes. These efficacy evaluations are necessary steps in the development of engineered bacteria as a drug entity, intending to effectively improve the stability of LBP efficacy.

5. Compared with other chemical drugs and biological products, live biotherapeutic products have a lower adverse reaction rate and good safety. Their safety risks primarily come from three aspects: potential adverse reactions in the digestive tract, metabolic products that cause toxicity, and the risk of infection. Therefore, researchers should fully consider these adverse reactions and emergencies, and prepare emergency plans for drug warnings during clinical trials.

In the future, with the cross-integration and infiltration of various technologies, live biotherapeutic products will overcome the current barriers hindering their development and benefit more patients, thus further promoting the development and application of microbial and synthetic biology, and other life sciences.

Creative Biolabs has abundant experience in helping our customers accelerate live biotherapeutics projects. If you are interested in our services, please feel free to contact us.

For Research Use Only. Not intended for use in food manufacturing or medical procedures (diagnostics or therapeutics). Do Not Use in Humans.