Poly(beta-amino ester)s as gene delivery vehicles: challenges and opportunities

ABSTRACT

Introduction

Gene delivery technologies are being developed for an increasing number of biomedical applications, with delivery vehicles including viruses and non-viral materials. Among biomaterials used for non-viral gene delivery, poly(beta-amino ester)s (PBAEs), a class of synthetic, biodegradable polymers, have risen as a leading gene delivery vehicle that has been used for multiple applications in vitro and in vivo.

Areas covered

This review summarizes the key properties of PBAEs and their development, including a discussion of the advantages and disadvantages of PBAEs for gene delivery applications. The use of PBAEs to improve the properties of other drug delivery vehicles is also summarized.

Expert opinion

PBAEs are designed to have multiple characteristics that are ideal for gene delivery, including their reversible positive charge, which promotes binding to nucleic acids as well as imparting high buffering capacity, and their rapid degradability under mild conditions. Simultaneously, some of their properties also lead to nanoparticle instability and low transfection efficiency in physiological environments. The ease with which PBAEs can be chemically modified as well as non-covalently blended with other materials, however, allows them to be customized specifically to overcome delivery barriers for varied applications.

KEYWORDS:

• Biomaterials
• gene delivery
• nanoparticles
• nucleic acids

Article highlights

• Materials for non-viral gene delivery must overcome many extracellular and intracellular barriers for successful transfection

• Poly(beta-amino ester)s (PBAEs) are cationic polymers designed to bind nucleic acids, promote cellular uptake and endosomal escape, and release polymers due to degradation

• PBAEs may be hampered by challenges, including their relative instability in physiological fluids and their potential to cause toxicity or immunogenicity due to excessive positive charge

• The ease with which PBAEs can be covalently and non-covalently modified allows them to be customized or blended with other materials to overcome delivery challenges and broadens their applicability

This box summarizes key points contained in the article.

Declaration of interest

S Y Tzeng is credited with inventorship on related patents received and pending. K R Rhodes is credited with inventorship on related pending patents. J J Green is also a Member of the Board of Directors, a Consultant, Co-Founder and holds Equity in Asclepix Therapeutics; A Managing Member, Co-Founder and holds Equity in Dome Therapeutics: is a Board of Directors Member, Consultant and holds Stock Options in VasoRX: is a Scientific Advisory Board Member and holds Stock Options in Tidal; and is an Investigator for AstraZeneca. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was supported by the National Institutes of Health (P41EB028239, R01CA228133, and R01EY031097), American Autoimmune-Related Diseases Association (grant support), and the National Science Foundation (fellowship support).