Congenital disease, estimated to cause the death of 276,000 infants within the first month of life each year across the globe, also causes childhood illness and long-term disability. Prenatal screening techniques now make early diagnosis possible, presenting the opportunity to intervene in disease processes before birth. Now, a study from researchers led by Rosalind Franklin University shows that antisense oligonucleotides (ASOs), short strands of engineered nucleic acid that are designed to bind to a specific gene-derived sequence, can be safely injected into the amniotic cavity, the fluid-filled sac that holds the embryo. The team state that their findings offer promise for therapeutic management of congenital diseases in utero using designer nucleotide sequences, that can simply be injected into the fluid surrounding the developing fetus to potentially treat disabling-to-lethal genetic defects. The opensource study is published in the journal Nucleic Acids Research.
Previous studies show that although there are some fetal interventions available for congenital structural defects using surgical interventions, there are few options for genetic disorders, which may have pathology beginning in utero. Antisense oligonucleotides (ASOs), which are short, modified nucleic acids designed to target and bind to a specific RNA sequences, are emerging as promising therapeutic molecules for congenital disorders. The favorable pharmacologic, pharmacokinetic and toxicological properties of ASOs make them a promising drug platform for disease therapeutics, though their safety and efficacy in utero is not known. The current study investigates whether deliver of ASOs to the mouse amniotic cavity can efficiently target gene expression.
The current study shows that intra-amniotic delivery of ASOs to mice embryos is well tolerated and produces a sustained effect on postnatal gene expression. Results show that an ASO targeting MALAT1 RNA, delivered by transuterine microinjection into the mouse amniotic cavity at embryonic day 13-13.5, reduces target RNA expression for up to 4 weeks after birth. Data findings show that an ASO targeting a causal splice site mutation for Usher syndrome corrects gene expression in the inner ear, a therapeutically relevant target tissue.
The lab state that the combination of a potentially low-risk delivery approach with the promising antisense drug platform, which, in theory, can alter any disease-associated aberrant gene expression by simply designing the sequence of the injectable molecule to match the target gene, is an exciting breakthrough; they stress that more work needs to be done to improve the efficiency of drug uptake and distribution to specific tissues. They go on to add that, to their knowledge, this study is the first demonstration of ASO embryonic transfer with amniotic fluid administration, or non-surgical insertion of ASOs into a developing fetus, a key step toward broad application of this powerful gene therapy approach in humans.
The team surmise that their findings suggest transuterine delivery of ASOs is an innovative platform for developing fetal therapeutics to efficaciously treat congenital disease. For the future, the researchers state that fetal ASO pharmacotherapy has the potential to safely enable therapeutic strategies for the treatment of fetal and congenital genetic disease.
Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.
Michelle has been picked up as an expert writer for Informa publisher’s Clinical Trials community, as well as being listed as a blog source by the world’s leading medical journals, including the acclaimed Nature-Springer journal series.
Healthinnovations is currently indexed by the trusted Altmetric and PlumX metrics systems, respectively, as a blog source for published research globally. Healthinnovations is also featured in the world-renowned BioPortfolio, BioPortfolio.com, the life science, pharmaceutical and healthcare portal.
Most recently the Texas A&M University covered The Top 10 Healthinnovations series on their site with distinguished Professor Stephen Maren calling the inclusion of himself and his team on the list a reflection of “the hard work and dedication of my students and trainees”.
Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.
An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.