Poly (beta‐amino ester) as an in vivo nanocarrier for therapeutic nucleic acids

Abstract

Therapeutic nucleic acids are an emerging class of therapy for treating various diseases through immunomodulation, protein replacement, gene editing, and genetic engineering. However, they need a vector to effectively and safely reach the target cells. Most gene and cell therapies rely on ex vivo gene delivery, which is laborious, time‐consuming, and costly; therefore, devising a systematic vector for effective and safe in vivo delivery of therapeutic nucleic acids is required to target the cells of interest in an efficient manner. Synthetic nanoparticle vector poly beta amino ester (PBAE), a class of degradable polymer, is a promising candidate for in vivo gene delivery. PBAE is considered the most potent in vivo vector due to its excellent transfection performance and biodegradability. PBAE nanoparticles showed tunable charge density, diverse structural characteristics, excellent encapsulation capacity, high stability, stimuli‐responsive release, site‐specific delivery, potent binding to nucleic acids, flexible binding ability to various conjugates, and effective endosomal escape. These unique properties of PBAE are an essential contribution to in vivo gene delivery. The current review discusses each of the components used for PBAE synthesis and the impact of various environmental and physicochemical factors of the body on PBAE nanocarrier.

Advances in Nonviral mRNA Delivery Materials and Their Application as Vaccines for Melanoma Therapy

“…134,142 New strategies continue to be developed to overcome these challenges and enhance PBAE-based therapeutic delivery. 143 To summarize, polymers are frequently used as mRNA delivery vehicles because they are structurally diverse and relatively easy to synthesize. Additionally, they can undergo various modifications, so their chemical and physical properties can be optimized for specific therapeutic applications.…”

“…PBAEs can also be chemically modified with ligands, peptides, and PEG to further reduce toxicity and improve selective delivery to specific organs. − To achieve controlled gene delivery, Lee and co-workers designed PBAEs that can be used for on-demand release of nucleic acids in response to UV light and pH triggers . However, PBAEs show some weaknesses as they can be unstable in physiological fluids and in long-term storage. , PBAEs also have relatively low binding efficiency to nucleic acids and can release nucleic acid cargo off-target. , New strategies continue to be developed to overcome these challenges and enhance PBAE-based therapeutic delivery …”

Growth factors and growth factor gene therapies for treating chronic wounds

“…Furthermore, transfection efficiency of PBAEs can be greatly influenced by the buffering system, imposing significant constraints on its widespread application. For instance, it was reported that in contrast to monovalent buffering systems, such as sodium acetate (NaAc), divalent buffering systems such as magnesium acetate and calcium acetate enhanced the transfection efficiency of PBAE‐based vectors 165 …”

Delivery of nucleic acids using nanomaterials

“…PBAE exhibits a highly adaptable chemical structure and is readily biodegradable. It can be synthesized by the Michael addition reaction [ 180 ]. The first attempt to use PBAE as a nucleic acid delivery vector was reported by Langer's team.…”