Polymeric Carriers for Delivery of RNA Cancer Therapeutics

Abstract

As research uncovers the underpinnings of cancer biology, new targeted therapies have been developed. Many of these therapies are small molecules, such as kinase inhibitors, that target specific proteins; however, only 1% of the genome encodes for proteins and only a subset of these proteins has ‘druggable’ active binding sites. In recent decades, RNA therapeutics have gained popularity due to their ability to affect targets that small molecules cannot. Additionally, they can be manufactured more rapidly and cost-effectively than small molecules or recombinant proteins. RNA therapeutics can be synthesised chemically and altered quickly, which can enable a more personalised approach to cancer treatment. Even though a wide range of RNA therapeutics are being developed for various indications in the oncology setting, none has reached the clinic to date. One of the main reasons for this is attributed to the lack of safe and effective delivery systems for this type of therapeutic. This review focuses on current strategies to overcome these challenges and enable the clinical utility of these novel therapeutic agents in the cancer clinic.

Advancing nucleic acid delivery through cationic polymer design: non-cationic building blocks from the toolbox

“…These units are either charged (e.g., tertiary amines) or neutral, and they can be incorporated during polymerization using multifunctional monomers or through post-modification methods, including crosslinking. 158,391 bPEI, PβAEs, PLL, PAMAM dendrimers present tertiary amines as branching points, and exhibit diverse amine groups with varying pK a values, enhancing NA binding and buffering capacity compared to linear polycations 142,[392][393][394] at the same M w . However, higher charge density may increase cytotoxicity due to cell membrane disrup- Polymer Chemistry Review tion.…”

Targeting miRNAs and Other Non-Coding RNAs as a Therapeutic Approach: An Update

“…Even though the immune system's activation may be advantageous in some circumstances, such as in response to vaccinations or immunotherapies, it may be harmful in other situations. Furthermore, because of their short half-lives due to fast degradation and renal clearance, the unfavorable pharmacokinetic profile of RNA therapies might impair their capacity to reach their desired site of action [122].…”