Optical Trap Methods to Determine the Viscoelastic Properties of Biological Materials

Optical traps (optical tweezers) have a focused laser beam able to trap a small bead at its focus, and are used to measure the microrheology of gels and other materials. They have recently been used to characterize properties of living cells, however issues of image spatial resolution and limited depth of interrogation have prevented application of an optical trap to measure microrheological (flow of matter) properties in complex (non-uniform) materials, such as multi-cellular systems or living organisms. 

Single Domain Antibodies (Nanobodies) Targeting SARS-CoV-2 for treating COVID-19

The COVID-19 pandemic is a worldwide public health crisis with over 100 million confirmed cases and 2.4 million deaths as of February 2021. COVID-19 is caused by a novel coronavirus called SARS-CoV-2. SARS-COV-2 infects hosts via its spike (S) protein. The S protein contains the receptor binding domain (RBD) that binds to the angiotensin converting enzyme 2 (ACE2) receptor on human cells to facilitate viral entry and infection. There are few therapeutics available for COVID-19 patients that directly target SARS-CoV-2.

High Affinity Monoclonal Antibodies Targeting Glypican-2 for Treating Childhood Cancers

Neuroblastoma is a rare pediatric cancer with approximately 1,000 new cases arising annually. Current therapies have a less than forty-five percent (45%), three-year survival rate which demonstrate a need for a more effective treatment against this disease. Glypican-2 (GPC2) is a cell surface protein that is preferentially expressed in pediatric cancers including neuroblastoma, which makes GPC2 an attractive candidate for targeted therapy. 
 

Single Domain Antibodies Targeting the S2 Subunit of SARS-CoV-2 Spike Protein

The COVID-19 pandemic is a worldwide public health crisis with over 100 million confirmed cases and 2.4 million deaths as of February 2021. COVID-19 is caused by a novel coronavirus called SARS-CoV-2. Almost all the neutralizing antibodies targeting SARS-CoV-2 that are in development recognize the receptor binding domain (RBD) on the spike (S) protein. Blocking the interaction of RBD and the ACE2 receptor on human cells is the first of the two critical steps for neutralization of the virus.

Nanobodies Neutralizing Lassa Virus

Lassa Hemorrhagic Fever (LHF) is a serious disease caused by infection with Lassa virus (LASV) – highly prevalent in West Africa and spreading globally. LASV is associated with high morbidity and mortality rates, annually infecting 100,000 to 300,000 individuals and causing 5,000 deaths. Developing prophylactics and treatment for LASV is difficult due to challenges in inducing neutralizing antibodies and producing their target, the LASV glycoprotein trimer (GPC).

High-Affinity Rabbit Monoclonal Antibodies for Cancer Treatment

Mesothelin is a cell surface protein that is highly expressed in aggressive cancers, such as malignant mesothelioma, ovarian cancer and pancreatic cancer, lung cancer, breast cancer, cholangiocarcinoma, bile duct carcinoma and gastric cancer.  Because of this selective expression, mesothelin is an excellent candidate for targeted therapeutics, such as monoclonal antibodies (mAbs) and chimeric molecules.  Current anti-mesothelin therapeutic mAb candidates bind to an epitope in Region I of mesothelin.  Unfortunately, Region I contains the interaction site MUC16/CA125, a mesothe

Synthetic Bacterial Nanoparticles as Drug and Vaccine Delivery Vehicles

Bacterial spores can be modified to display molecules of interest, including drugs, immunogenic peptides, antibodies and other functional proteins of interest (such as enzymes).  The resulting engineered bacterial spores can provide many useful functions such as the treatment of infections, use as an adjuvant for the delivery of vaccines, and the enzymatic degradation of environmental pollutants.

Increased Therapeutic Effectiveness of PE-Based Immunotoxins

Patients receiving immunotoxin cancer therapy are less likely to experience the deleterious side-effects associated with non-discriminate therapies such as chemotherapy or radiation therapy. Unfortunately, the continued administration of immunotoxins often leads to a reduced patient response due to the formation of neutralizing antibodies against immunogenic epitopes contained within Pseudomonas exotoxin A (PE). 

Gene Therapy for Treatment of CRX-Autosomal Dominant Retinopathies

Mutations in the cone rod homeobox (CRX) transcription factor lead to distinct retinopathy phenotypes, including early-onset vision impairment in dominant Leber congenital amaurosis (LCA). Adeno-Associated virus (AAV) vector-mediated delivery of a CRX cDNA under the control of a CRX promoter region partially restored photoreceptor phenotype and expression of phototransduction genes in an in vitro model of CRX-LCA.

Induced Pluripotent Stem Cells Derived from Patients with CEP290-associated Ciliopathies and Unaffected Family Members

Approximately one-third of non-syndromic retinal dystrophies involve a defect in a ciliary protein. Non-syndromic retinal ciliopathies include retinitis pigmentosa, cone dystrophy, cone-rod dystrophy, macular dystrophy, and Leber-congenital amaurosis (LCA). Many CEP290-LCA patients also exhibit auditory and olfactory defects. Induced pluripotent stem cells (iPS) cells were derived from patients with LCA and unaffected relatives. 
The National Eye Institute (NEI) seeks research collaborations and/or licensees for the use of these iPS cells.