DDW Editor Reece Armstrong speaks to Dr Sandro Ataide, Senior Lecturer in Structural Biology at the School of Life and Environmental Sciences Sydney Drug Discovery Initiative (DDI).

Earlier this year, Dr Ataide’s team developed a gene-editing tool called SeekRNA that uses a programmable ribonucleic acid (RNA) strand that can directly identify sites for insertion in genetic sequences, potentially simplifying the editing process and reducing errors.

Here, Dr Ataide outlines the tool’s advantages over CRISPR and what it means for drug discovery. 

RA: Could you reflect upon some of the advances we’ve seen come from CRISPR in regards to drug discovery and development in the past 10 years?

SA: CRISPR has transformed drug discovery through its profound impact in accelerating the genetic engineering field to develop important cell lines for drug screening which have been translated to clinical treatment and development of immunotherapy and CAR-T cells, along with cures of genetic diseases. The broad impact of CRISPR in the past 10 years expands far beyond the medical area but through all biological fields.

RA: What are the major limitations of genetic editing technologies? 

SA: Some of the limitations are the size of DNA that can be inserted which can reach up to a few kilobases. The size of the CRISPR components makes the delivery to different cell types and organisms difficult and very limited. Another limitation is the undesired off-targeted effect which has a profound impact in translation to clinical use. 

RA: What benefits does SeekRNA offer over CRISPR?

SA: SeekRNA has much smaller components which can facilitate the delivery to cells using multiple approaches. The seekRNA can be reprogrammed to tolerate less mismatches and less off-target effects. Additionally, the flexible size of the DNA that is directly inserted into the desired target does not require the recruitment of the cellular machinery like CRISPR does. 

RA: How confident are you that SeekRNA will translate into complex eukaryotic cells found in humans? 

SA: CRISPR has opened the way in teaching us how to translate technologies to eukaryotic cells. We will follow their lead and make any required changes to get it working, and then improve upon it.

RA: Does SeekRNA have the same ethical concerns that surround genetic editing technologies?

SA: There are two sides of the ethical concerns – efficacy/safety – and – ecological/social – imbalance. SeekRNA may overcome the efficacy/safety concerns however the ecological/social imbalance will follow the same regulations. 

RA:  How beneficial is it that SeekRNA can use only a single protein for its application? 

SA: Compact systems, like SeekRNA, can be delivered to cells using different methods and we expect to explore this to expand its usage. CRISPR system requires multiple proteins which limits its delivery and wide-range of applications.

RA: How does the size of the SeekRNA system benefit drug delivery? 

SA: It can be used in conjunction with drug delivery and hopefully used in gene therapies using newly developed and approved methods and achieving clinical use  which has not been possible yet with other technologies. 

RA: What advantages does direct insertion into DNA bring?

SA: It minimises errors and reduce the indels on the target site. The precision of the direct insertion of DNA makes it safer and less error prone system.

RA: What advances could SeekRNA bring? 

SA: Hopefully an easy transition to clinical use for gene therapies along with many other usages. Certainly we will see a new era in genetic engineering and treatments after further development and applications of the SeekRNA.

From DDW Volume 25 – Issue 4, Fall 2024 Read the digital issue

Biography:

Sandro F Ataide is a biochemist and structural biologist at the School of Life and Environmental Sciences at the University of Sydney since 2012. He completed his PhD at The Ohio State University. He was a post-doc at UC Berkeley and at ETH in Zurich. His research on the structural and biochemical characterisation of RNAs and RNA-protein complexes discovered a new gene editing tool named seekRNA.