LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

Antibody-siRNA conjugates: drugging the undruggable for anti-leukemic therapy

Photo from wikipedia

ABSTRACT Introduction: Generating effective RNAi-based therapies with the potential to achieve leukemia remission remains critical unmet need. Despite a growing number of leukemia clinical trials, tissue specific delivery of therapeutic… Click to show full abstract

ABSTRACT Introduction: Generating effective RNAi-based therapies with the potential to achieve leukemia remission remains critical unmet need. Despite a growing number of leukemia clinical trials, tissue specific delivery of therapeutic siRNA is a major roadblock in translating its clinical potential. The most recent reports in the antibody-siRNA-conjugates (ARCs) field add new dimensions to leukemic therapy, where a covalently ligated therapeutic antisense-RNA with the potential to repress the oncogenic transcript is selectively delivered into the cancer cells. Despite ARC localization to leukemic cells due to high affinity antigen-antibody interactions, multiple challenges exist to unlock the therapeutic potential of siRNA targeting. Areas covered: This review focuses on antibody and siRNA-based therapies for leukemia as well as potential antibody engineering-based strategies to generate an optimal ARC platform. Expert opinion: In vitro and clinical results have revealed that non-targeted delivery and inefficient cellular internalization of therapeutic siRNA are major contributing factors for the lack of efficacy in leukemia patients. Rational antibody design and selective protein engineering with the potential to neutralize siRNA charge, stabilize ARC complex, restrict off-targeted delivery, optimize endosomal escape, and extend serum half-life will generate clinically relevant leukemic therapies that are safe, selective, and effective.

Keywords: therapy antibody; sirna conjugates; antibody sirna; leukemic therapy; antibody

Journal Title: Expert Opinion on Biological Therapy
Year Published: 2017

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.