
Dr. Bikash Pattnaik’s groundbreaking approach to genetic blindness
In this interview, Dr. Bikash Pattnaik from the University of Wisconsin-Madison talks about his groundbreaking gene therapy and how ion channel research sheds light on rare eye conditions causing vision loss.
Could you tell us about your laboratory, its mission, and your research?
Our lab in the University of Wisconsin has a research focus on the study of ion channel physiology in the retina. We place a special emphasis on genetic mutations in ion channel genes that alters retina physiology causing blindness.
What is the nature of your scientific work? How did you find yourself at the intersection of ion channel research, gene therapy, and ophthalmology?
I was trained for my PhD working on structure-function relationships of a bacterial outer membrane porin that plays an important role in drug resistance. My post-doctoral work exposed me to GABA receptors in the outer retina. I got interested in ion channel function and dysfunction in the retina. We studied Inwardly rectifying potassium channel in the retinal pigment epithelium that was endogenously regulated by phosphoinositide. That’s the time it was reported that genetic mutations in this channel protein gene cause inherited retinal degeneration. We also discovered novel nonsense mutations that caused retinal dystrophy. Since this was a monogenic disease, we routinely study ion channel function by exogenous expression. Gene therapy for retinal diseases is leading the field, and I got interested in developing gene therapy for the mutation that we studied. Also, studying a nonsense mutation model provided us with certain advantages of novel drug discovery/testing compared to opportunities provided by other mutations
Can you share with us some of your latest research findings and discoveries?
Our genomic medicine effort is multipronged approach to determine potential functional therapeutic outcome. We have successfully developed gene therapy for monogenic Leber Congenital Amaurosis (LCA16) PMID: 30686507 and 35096838. Gene therapy for Best Vitelliform Macular Degeneration (BVMD) disease PMID: 32707085. Genome editing to rescue Kir7.1 function (PMID: 37561581) and Best disease Ca2+ activated Cl- channel (PMID: 32707085). Readthrough of nonsense mutation using small molecules and biologics (Invest. Ophthalmol. Vis. Sci.. 2024; 65(7):6092, Invest. Ophthalmol. Vis. Sci.. 2023; 64(8):414, and Invest. Ophthalmol. Vis. Sci.. 2021; 62(8):209).

Copied from Kabra et al., J. Clin. Invest., 2023.
You have various electrophysiological patch clamp solutions in your laboratory. Could you describe your patch clamp electrophysiology workflow in your laboratory?
Our electrophysiology expertise is in our approach from the single cells to tissue to animal physiology validation of our hypothesis. For single cell electrophysiological patch clamp studies, we first use heterologous expression through plasmid transfection followed by whole-cell recording. This allows us to establish channel properties and assay development that can be translated to studies using primary cells or human induced pluripotent stem cells derived retinal cells. This helps us to establish protocols for automated patch-clamp analysis where we can reproduce manual electrophysiology standards and obtain high through put outcome.
What are the benefits of using automated patch clamp solutions as part of your research?
One of the key benefits for us is not just the increase in the throughput but for genome editing projects as there is cell to cell variation, we anticipated that manual patch clamp will be challenging to determine outcome. The other advantage is the study of iPSC cells. These cells are often grown for more than 200 days in culture, and we wanted to maximize study outcome by using automated patch clamp.
Where do you see or want the lab’s work going in the next few years?
We have already used our labs gene therapy for clinical development through Hubble Therapeutics. We intend to see also our genome editing and read through therapies get translated to the clinic.
To discover more about Dr. Bikash Pattnaik’s work on gene therapy and retinal research: