Treating blood disorders like sickle cell anaemia and haemophilia poses a significant challenge due to their diverse origins. Fortunately, a technology that is effective and safe in COVID-19 vaccines may hold the key to treating such conditions cost-effectively and non-invasively.
Messenger RNA (mRNA) therapies have been harnessed for their ability to target cells and deliver healing instructions. In an experiment on rodents, published in the journal Nano Letters, researchers from the Massachusetts Institute of Technology combined mRNA with c-kit antibody-targeted lipid nanoparticles (LNPs) to target hematopoietic stem cells (HSCs) that are responsible for blood cell production.
The LNPs carrying the biological instructions were then attached to the c-kit receptor on HSCs. They provided an efficient method to deliver gene therapy, promising to treat genetic blood disorders and other conditions.
Targeted delivery
“This targeted delivery system eliminates the need for stem cell harvesting, culture, or patient conditioning, providing a potentially more efficient and cost-effective approach for gene therapy,” said the study’s lead author Dennis Shi from the Massachusetts Institute of Technology in the United States.
Others too agreed on the method’s capability of designing personalised therapies using RNA and LNPs to target specific mutations in DNA.
“This advanced technology has proven successful in the development of COVID vaccines and shows promise for treating blood disorders like sickle cell anaemia and haemophilia,” said Dharmesh Patel, associate director of Cell Therapy and Gene Editing Process Development at the Center for Breakthrough Medicines in the United States.
The authors of the study found that the LNPs delivered mRNA have a gene editing efficiency of 90 per cent in both HSCs and long-term hematopoietic stem cells (LT-HSCs).
LT-HSCs can renew themselves for a long period of time.
Not just mending genetic mutations
While mRNA therapies can deliver instructions to mend genetic mutations, RNA interference technologies such as siRNA and miRNA can reduce gene expression to counter the effect of mutations.
“siRNA and miRNA technologies offer effective gene knockdown and targeted delivery to specific tissues,” adds Patel.
siRNA or small interfering RNA and miRNA are small RNA molecules that play essential roles in gene regulation by suppressing or silencing specific genes. While siRNA is typically used to target a single gene mutation, miRNA can be used to regulate multiple gene mutations.
Nonviral LNPs offered superiority over traditional adenoviruses
Nonviral delivery systems like LNPs provide an exciting alternative to traditional adenoviruses to deliver genetic modifications. The study’s results are promising, with the optimised formulation of the antibody-targeted LNPs surpassing past experiments.
“RNA LNP biology offers a nonviral alternative with better prospects for efficient and targeted delivery. This exciting field presents new possibilities for improving treatments while maintaining affordability,” says Patel. He highlights the limitations of using viruses as vectors in delivering genetic therapies. They include size constraints and potential immune response.
Detecting mutations in blood disorders
The advancement can not only improve treatments of genetic blood disorders but also aid in their detection. Currently, scientists rely on techniques like complete genomic sequencing to identify genetic mutations responsible for blood disorders. This involves comparing every “letter” in our genes to a reference version to pinpoint potential changes causing the disorder.
Advances in probe-based targeting could change this with the use of special tools that act like searchlights, scanning specific genes related to the blood disorder for changes. Others include CRISPR to target specific mutations in our DNA, assisted by a guide called gRNA.
Once CRISPR identifies the problem, custom-designed mRNA carrying the corrected genetic information to allow the cell to perform optimally is inserted. This powerful collaboration between CRISPR and mRNA brings renewed hope for improved treatments in the realm of genetic disorders.
Advances such as these and in areas such as customisable mRNA therapies can revolutionise blood disorder treatment. Currently, c-kit antibody-targeted LNPs may be a leading contender for precise RNA delivery to HSCs.
