Development of targeted delivery system for saRNAs using SNAP tag-based antibody fusion protein to treat triple-negative breast cancer

Triple negative breast cancer (TNBC) is a highly invasive and heterogenous disease that does not express oestrogen receptor and progesterone as well as the human epidermal growth factor receptor-2 and accounts for approximately 20% of all breast tumors. Its heterogenicity makes unlikely to reach the complete TNBC patient population with a single therapeutic agent. Therefore, corresponding receptors differentially overexpressed are being considered as high potential diagnostic/therapeutic targets, for example the ADC Sacituzumab govitecan (SG) approved by the FDA. However, ADCs are often with the off-target toxicities of the toxins. An elegant approach is to use self-amplifying RNAs (saRNAs). The aim of this research is to decorate nanoparticles with snap-tag based antibody fusion proteins for targeted delivery for TNBC treatment.
The saRNA encoding sequence will be cloned into a backbone plasmid vector. The linearized vector containing saRNA encoding eGFP will be transcribed and purified. The purified saRNA encoding eGFP will be encapsulated into a lipid nanoparticle using a microfluidic system, followed by characterization. After characterization, the lipid nanoparticle will be transfected into mammalian HEK293T cells. Upon successful transfection, the saRNA encoding eGFP encapsulated in the lipid nanoparticle will be used for cytotoxicity assay on TNBC positive cell line.

Faculty Supervisor:

Anna Blakney

Student:

Partner:

University of Cape Town

Discipline:

Life Sciences

Sector:

Health and Related Sciences & Technology; Biotechnology

University:

The University of British Columbia

Program: