"Unlocking Hope: Exploring Treatment Innovations for Potocki Lupski Syndrome
Welcome to our dedicated space where we delve into the forefront of scientific exploration aimed at conquering Potocki Lupski Syndrome.
Our team is devoted to pioneering diverse methods and innovative approaches in the quest for effective treatments.
Join us as we explore a spectrum of promising methodologies, from groundbreaking gene therapies and targeted molecular interventions, to novel pharmaceutical advancements, aiming to pave the way towards transformative treatment breakthroughs.
ASO - Antisense Oligonucleotides Therapy
An ASO is a small string of DNA or RNA letters that can stick to the mRNA. While they act on genetic diseases, ASO’s are not considered ‘gene therapy’ as they only make contact with RNA, not DNA. There are two types of ASO’s: splice-modulating and knockdown. For Potocki Lupski Syndrome we will be exploring ASO Knockdown.
Knockdown ASO’s work by connecting to the mRNA and silencing the message by activating an enzyme that degrades the RNA. Knockdown ASO’s work best for dominant diseases in which a gene makes too much of a protein or makes a toxic protein. These ASO’s help decrease the amount of protein to a level the body can manage.
“we Hope to be able to drastically reduce or ‘knockdown’ the over expression of the RAi1 gene which is duplicated in those with Potocki Lupski Syndrome, causing an over expression of the protein to be expressed in the brain”
Study finds antisense oligonucleotides to treat MECP2 disorder -
Gene Therapy - Small Molecules
The correct functioning of cells relies heavily on the ability to finely control gene expression, a complex process by which the information contained in DNA is copied into RNA to eventually give rise to all the proteins and most of the regulatory molecules in the cell. If DNA can be imagined as a dense technical manual, gene expression is the method by which the cell extracts useful information from it.
Researchers have unveiled how this process can be modulated using small molecules. The study lays the groundwork for the future identification of potential drugs that act directly on genetic mutations or modifications which alter the process of gene expression.
“Small molecules offer an important alternative with potential for oral bioavailability and blood–brain barrier penetrance”
Modulating gene expression using small molecules
Drug Discovery
A drug discovery programme initiates because there is a disease or clinical condition without suitable medical products available and it is this unmet clinical need which is the underlying driving motivation for the project. The initial research, often occurring in academia, generates data to develop a hypothesis that the inhibition or activation of a protein or pathway will result in a therapeutic effect in a disease state. In this case, inhibition of the over expression of RAI1 in those with Potocki Lupksi Syndrome
The outcome of this activity is the selection of a target (RAI1)which may require further validation prior to progression into the lead discovery phase in order to justify a drug discovery effort. During lead discovery, an intensive search ensues to find a drug-like small molecule or biological therapeutic, typically termed a development candidate, that will progress into preclinical, and if successful, into clinical development and ultimately be a marketed medicine.
The benefits of drug discovery include that doses can be tritiated to individuals and the effects will not be permanent allowing observation of desired effects
info taken from NIH*
CRISPR
CRISPR gene editing is a genetic engineering technique in molecular biology by which the genomes of living organisms may be modified. It is based on a simplified version of the bacterial CRISPR-Cas9 antiviral defence system. By delivering the Cas9 nuclease complexed with a synthetic guide RNA(gRNA) into a cell, the cell's genome can be cut at a desired location, allowing existing genes to be removed and/or new ones added in vivo.
The technique is considered groundbreaking in biotechnology and medicine as it enables editing genomes in vivo very precisely and easily.
“We Hope to remove the RAi1 duplicated gene that is the known cause of Potocki Lupski Syndrome with CRISPR, and therefore rebalancing the gene expression to a normal level, and In a best case scenario we hope to remove the entire duplication“ .
FDA Approves First Gene Therapies
RNA
RNA therapeutics work by manipulating the expression and activity of specific target molecules, providing the means to treat diseases that do not respond to conventional drug types.
Several techniques, called RNA therapies, use pieces of RNA, which is a type of genetic material similar to DNA, to help treat a disorder. In many of these techniques, the pieces of RNA interact with a molecule called messenger RNA (or mRNA for short). In cells, mRNA uses the information in genes to create a blueprint for making proteins. By interacting with mRNA, these therapies influence how much protein is produced from a gene, which can compensate for the effects of a genetic alteration. Examples of these RNA therapies include antisense oligonucleotide (ASO), small interfering RNA (siRNA), and microRNA (miRNA) therapies. An RNA therapy called RNA aptamer therapy introduces small pieces of RNA that attach directly to proteins to alter their function.
Promising new RNA editing technology could be used to treat genetic diseases
SeekRNA
Patented method developed in the laboratory of Dr Sandro Ataide promises to accelerate the potential of genetic engineering already shown by CRISPR gene-editing technology. Scientists at the University of Sydney have developed a gene-editing tool with greater accuracy and flexibility than the industry standard, CRISPR, which has revolutionised genetic engineering in medicine, agriculture and biotechnology.SeekRNA uses a programmable ribonucleic acid (RNA) strand that can directly identify sites for insertion in genetic sequences, simplifying the editing process and reducing errors.
The new gene-editing tool is being developed by a team led by Dr Sandro Ataide in the School of Life and Environmental Sciences. Their findings have been published in Nature Communications.“We are tremendously excited by the potential for this technology. SeekRNA’s ability to target selection with precision and flexibility sets the stage for a new era of genetic engineering, surpassing the limitations of current technologies,” Dr Ataide said.
seekRNA delivers a new pathway for accurate gene editing
AAV - Gene Therapy
Adeno-Associated Virus (AAV) as a Vector for Gene Therapy, There has been a resurgence in gene therapy efforts that is partly fueled by the identification and understanding of new gene delivery vectors. Adeno-associated virus (AAV) is a non-enveloped virus that can be engineered to deliver DNA to target cells, and has attracted a significant amount of attention in the field, especially in clinical-stage experimental therapeutic strategies. The ability to generate recombinant AAV particles lacking any viral genes and containing DNA sequences of interest for various therapeutic applications has thus far proven to be one of the safest strategies for gene therapies.
Evolving AAV-delivered therapeutics towards ultimate cures
shRNA/miRNA
RNAi offers researchers an effortless tool for investigating biological systems by selectively silencing genes. Key technical aspects--such as optimization of selectivity, stability, in vivo delivery, efficacy, and safety--need to be investigated before RNAi can become a successful therapeutic strategy. Nevertheless, this area shows a huge potential for the pharmaceutical industry around the globe.
siRNA, miRNA, and shRNA: in vivo applications
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