Expanding the Reach of Monoclonal Antibodies: A Review of Synthetic Nucleic Acid Delivery in Immunotherapy

Abstract

Harnessing the immune system to combat disease has revolutionized medical treatment. Monoclonal antibodies (mAbs), in particular, have emerged as important immunotherapeutic agents with clinical relevance in treating a wide range of diseases, including allergies, autoimmune diseases, neurodegenerative disorders, cancer, and infectious diseases. These mAbs are developed from naturally occurring antibodies and target specific epitopes of single molecules, minimizing off-target effects. Antibodies can also be designed to target particular pathogens or modulate immune function by activating or suppressing certain pathways. Despite their benefit for patients, the production and administration of monoclonal antibody therapeutics are laborious, costly, and time-consuming. Administration often requires inpatient stays and repeated dosing to maintain therapeutic levels, limiting their use in underserved populations and developing countries. Researchers are developing alternate methods to deliver monoclonal antibodies, including synthetic nucleic acid-based delivery, to overcome these limitations. These methods allow for in vivo production of monoclonal antibodies, which would significantly reduce costs and simplify administration logistics. This review explores new methods for monoclonal antibody delivery, including synthetic nucleic acids, and their potential to increase the accessibility and utility of life-saving treatments for several diseases.

A Comprehensive Review of Monoclonal Antibodies in Modern Medicine: Tracing the Evolution of a Revolutionary Therapeutic Approach

“…Personalized medicine and targeted therapies stand as pioneering approaches in contemporary healthcare, particularly within the sphere of oncology. Personalized medicine entails tailoring medical interventions based on an individual's genetic makeup and unique characteristics, thereby enabling more precise and efficacious treatments with diminished side effects [53,54]. Also known as precision medicine, this approach leverages genetic information to craft treatments that specifically target the distinct genetic attributes of a patient's cancer, resulting in enhanced outcomes and mitigated adverse effects [53].…”

Recent Advances in the Development of Monoclonal Antibodies and Next-Generation Antibodies

“…The DNA-encoded mAb approach delivers genetic constructs expressing the desired mAbs within the host cells, eliminating the need for customary manufacturing and purification processes. Viral vectors, especially adeno-associated virus (AAV), have been used successfully for mAb delivery ( 41 ). AAV can infect both quiescent and actively proliferating cells without integrating into the host cell’s DNA.…”

Pharmacokinetic Analyses of a Lipid Nanoparticle-Encapsulated mRNA-Encoded Antibody against Rift Valley Fever Virus

“…Therapeutic antibodies have additional advantages over vaccines for the prevention and treatment of infectious diseases because antibodies have a remarkable safety record and can be developed faster and safer than vaccines, which generally take much longer, even decades, to develop and can be used at any age or in immunocompromised populations. 7 Therapeutic antibodies through injection of antibodies have the potential for an almost immediate effect compared to vaccines, which usually take weeks to provide protection. However, one of the barriers to using antibodies to treat infectious diseases is the complexity and high cost of producing recombinant antibody proteins, which are complex and expensive to produce and are likely to be produced commercially at a much lower cost than equivalent protein therapies.…”

“…Therapeutic antibodies have additional advantages over vaccines for the prevention and treatment of infectious diseases because antibodies have a remarkable safety record and can be developed faster and safer than vaccines, which generally take much longer, even decades, to develop and can be used at any age or in immunocompromised populations . Therapeutic antibodies through injection of antibodies have the potential for an almost immediate effect compared to vaccines, which usually take weeks to provide protection.…”