A Natural Answer: Biologics 101

The term biologic refers to a diverse group of agents that are produced/obtained from biological sources and/or contain biological components. Much like synthetic pharmaceutical agents, biologics are investigated and developed with the aim of targeting and rectifying pathological mechanisms in the human body. However, while synthetic pharmaceuticals mainly affect cellular signaling through the modulation of receptor-ligand interactions, biologics can exert their effects in a myriad of ways through numerous different mechanisms. Biologic agents currently being used for research and therapeutic purposes range from molecules and peptides (e.g., antibodies and hormones), to intact and functional cells (e.g., stem cells), to 3-D structures such as tissues and organs. Because of this diversity, a firm and comprehensive understanding of how biologic agents will behave in different physiological and pathological conditions (e.g., environments, locations, and cell types) is critical to their effective usage and the prevention of side effects.

Small but mighty: molecular biologics

Molecular agents are perhaps the biologics most similar to traditional pharmaceuticals, since both classes of agents function by directly modulating cellular mechanisms. However, molecular biologics are capable of a much wider range of targets and effects. For example, antibodies can interact with any potential antigen – not only surface receptors – to promote a desired cell-cell interaction, while hormones and cytokines can modulate not only cellular function, but also induce more systemic effects such as microenvironment condition changes. 

Changing blueprints: genetic biologics

One major difference between pharmaceuticals and biologics is their relative abilities to interact with genetic elements. Pharmaceuticals can indirectly induce changes at the genomic or transcriptional level by up- or downregulating cell signaling pathways that affect transcriptional regulators such as NF-κB. In contrast, biologic agents can include genes and/or gene sequences that integrate into the genome, nucleic acid structures/sequences that directly interact with translational products (e.g., DNA/RNA interference), and gene editing machinery (e.g., CRISPR, Cre recombinase) that can be activated when desired. In this way, biologics can directly modulate the expression and/or transcription of existing genes and change the genome through the addition or alteration of genetic sequences. 

Another dimension: cellular and tissue biologics

Much of the excitement surrounding biologics is their potential to not only modulate existing mechanisms, but also to generate de novo cells and tissues. Initial investigations on whether extracted or cultured cells could be introduced into the body for therapeutic purposes were met with limited success, but improved understanding of cellular behavior, gene editing, and stem cell technology have resulted in the development of new custom engineered cells for both therapeutic and research aims. These cells can now be used as agents themselves for adaptive cell therapy research, they can serve as disease models or cellular factories for the production of other biologics, or they can be placed in combination with other cells on synthetic or biologic scaffolds in tissue engineering research. 

Ever forward: the potential of biologics

The conception, production, and usage of biologics has both emerged from – and contributed significantly to – our understanding of biological systems under physiological and pathological conditions. Biologics represent a way forward that is more closely aligned with natural pathways and mechanisms, and in doing so offers researchers more relevant models and more accurate data in their quest to better understand the diseases and health care obstacles afflicting the population.

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