Lisa N Kasiewicz studies advanced gene-editing techniques to treat conditions related to cholesterol and liver function. Specifically, she explores how to deliver CRISPR therapy effectively to the liver using lipid nanoparticles that are designed to bypass the usual cellular roadblocks. This is particularly important for individuals suffering from genetic disorders like homozygous familial hypercholesterolemia, where traditional treatments may not be effective. Through her research, she aims to provide long-lasting solutions that could eliminate the need for daily cholesterol medications.
Key findings
Through the use of GalNAc-lipid nanoparticles, liver editing increased from 5% to 61% in monkeys, achieving up to an 89% reduction of a cholesterol-related protein six months after treatment.
A single injection of CRISPR therapy resulted in a 60% drop in cholesterol levels in primates, which remained low for at least 8 months without further treatment.
This innovative approach offers a potential one-time solution for patients with high cholesterol, reducing reliance on lifelong medications.
Frequently asked questions
Does Dr. Kasiewicz study high cholesterol?
Yes, Dr. Kasiewicz focuses on gene-editing therapies to lower cholesterol levels, making it a major part of her research.
What treatments has Dr. Kasiewicz researched?
She has researched CRISPR-based gene editing techniques delivered via lipid nanoparticles to treat high cholesterol and liver disorders.
Is Dr. Kasiewicz's work relevant to patients with liver disorders?
Absolutely, her research targets patients with liver-related issues, particularly those who can't use traditional cholesterol treatments.
Publications in plain English
Amine headgroups in ionizable lipids drive immune responses to lipid nanoparticles by binding to the receptors TLR4 and CD1d.
2024
Nature biomedical engineering
Chaudhary N, Kasiewicz LN, Newby AN, Arral ML, Yerneni SS +7 more
Plain English This study looked at how certain lipids in lipid nanoparticles (LNPs), which are used to deliver RNA therapies, affect the immune system. The researchers found that the amine parts of these lipids trigger immune responses by interacting with specific immune receptors. This interaction leads to an increase in certain immune proteins and helps maintain the effectiveness of LNPs in delivering therapeutic RNA without losing efficacy due to immune reactions.
Who this helps: This helps patients receiving RNA-based treatments, as it may lead to more effective delivery methods.
GalNAc-Lipid nanoparticles enable non-LDLR dependent hepatic delivery of a CRISPR base editing therapy.
2023
Nature communications
Kasiewicz LN, Biswas S, Beach A, Ren H, Dutta C +13 more
Plain English This study focused on a new way to deliver a CRISPR therapy to the liver using special nanoparticles that don't rely on a common receptor that some patients lack. The researchers found that by modifying these nanoparticles, they could increase liver editing from 5% to 61% in certain monkeys, and this treatment led to a significant decrease in a specific protein related to cholesterol levels, achieving reductions of up to 89% six months later. This matters because it provides a potential treatment option for patients who cannot use traditional methods due to their genetic conditions.
Who this helps: Patients with homozygous familial hypercholesterolemia and other liver-related disorders.
In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates.
2021
Nature
Musunuru K, Chadwick AC, Mizoguchi T, Garcia SP, DeNizio JE +37 more
Plain English Researchers used a gene-editing tool called CRISPR to permanently disable a gene in monkeys' livers that controls cholesterol production, delivering it through tiny fat particles injected into the bloodstream. After a single injection, the monkeys' cholesterol dropped by about 60% and stayed low for at least 8 months without any additional treatment. This proves that gene editing could offer heart disease patients a one-time treatment instead of taking cholesterol drugs for life.
Lipid nanoparticles silence tumor necrosis factor α to improve wound healing in diabetic mice.
2019
Bioengineering & translational medicine
Kasiewicz LN, Whitehead KA
Plain English This study looked at a new treatment for wounds in mice with diabetes, focusing on a substance called tumor necrosis factor α (TNFα) that makes healing slower. The researchers used tiny particles to deliver a molecule that reduces TNFα levels, which resulted in a 40-55% decrease in TNFα in the wounds and helped wounds heal faster in diabetic mice compared to those that didn't receive the treatment. This finding is significant because it shows that this approach could potentially improve healing for people with diabetes who struggle with chronic wounds.
Who this helps: Patients with diabetes, especially those suffering from slow-healing wounds.
Recent advances in biomaterials for the treatment of diabetic foot ulcers.
2017
Biomaterials science
Kasiewicz LN, Whitehead KA
Plain English This research focuses on new materials designed to help heal diabetic foot ulcers, which are common and serious problems for people with diabetes. The study found that these advanced materials can boost healing by improving the growth of new blood vessels and tissue, reducing inflammation, and controlling the delivery of helpful drugs. This is important because it can lead to faster healing and better overall health for diabetes patients.
Who this helps: Patients with diabetes who suffer from foot ulcers.
Silencing TNFα with lipidoid nanoparticles downregulates both TNFα and MCP-1 in an in vitro co-culture model of diabetic foot ulcers.
2016
Acta biomaterialia
Kasiewicz LN, Whitehead KA
Plain English This study looked at how a new therapy using tiny particles called lipidoid nanoparticles can reduce two harmful proteins (TNFα and MCP-1) in diabetic foot wounds, which are often difficult to heal. By using this therapy, the researchers found that TNFα levels dropped by 64% and MCP-1 levels decreased by 32%, helping to potentially improve the healing process for these wounds. This matters because diabetic foot ulcers are a growing problem and current treatments are not very effective, so a new solution could greatly benefit patients.
Who this helps: Patients with diabetic foot ulcers.