Oiling DNA nanocages with lipid molecules makes them slide through cell membranes

Work done in the lab of Prof. Dhiraj Bhatia at IIT Gandhinagar

About author

Dr. Ramesh Singh grew up in a small village Kwairala in the Almora district of Uttarakhand where he received his primary education. He completed his bachelor and Master (Organic Chemistry) from MB Govt. PG College, Haldwani, affiliated with Kumaun University Nainital. He passed UGC NET-JRF and GATE with merit. With this Doctoral Fellowship, he joined Dr. K B Joshi’s research group at Dr. Harising Gour Vishwavidyalaya Sagar, Madhya Pradesh, and earned his Ph.D. in Bio-Organic Chemistry. At present, he is pursuing his research as a postdoctoral fellow at the Indian Institute of Technology Gandhinagar under the supervision of Dr Dhiraj Bhatia. Dr Singh is a biochemist and is actively involved in the synthesis of self-assembling biomaterial using biomolecules such as peptides, Nucleic acid and lipids.

Interview

How would you explain your research outcomes to the non-scientific community?

DNA biomolecules occupy an extraordinary role in biology as a carrier of genetic information. Using these molecules, we can create containers at nanometer scale known as DNA nanocages. These cages are capable of loading and transporting drugs and medicines and delivering them to the precise location where they are needed. However, structural barriers and repulsive forces by cell membranes prevented them from entering the mammalian cells.

In this study, our team identified and optimized a cationic lipid molecule that has an affinity towards both DNA nanocages and cell membranes. We masked the DNA nanocages with these lipid molecules so that they can easily cross the cell membrane. Through this method of functionalization of the DNA nanocages, we addressed the structural barrier, thereby increasing the cellular absorption of nanocarriers in sufficient quantities to be employed for drug delivery.

How do these findings contribute to your research area?

In medication administration, a cellular plasma membrane acts as a natural barrier to safeguard extremely sensitive intracellular organelles. Therefore, considerable modifications are necessary for maximum cellular absorption in order to increase the effectiveness of the therapeutic action. We provided a practical approach to functionalize DNA nanostructures with a cationic lipid in order to improve the cellular absorption of these nanocarriers. We demonstrated a straightforward confocal microscopy-based method to visualize the improvement in DNA nanocage uptake by cells. It is suggested that it might be used with various nanocarrier systems for successful cell membrane internalization, which would help with the development of efficient bioimaging and drug delivery/transfection systems.

“We provided a practical approach to functionalize DNA nanostructures with a cationic lipid in order to improve the cellular absorption of these nanocarriers. “

What was the exciting moment during your research?

As a scientist, I always find chemistry intriguing, even when I use a very simple approach. Although the synthesis of nanocages has already been documented, I performed it for the first time for this work. The synthesis of nanocages utilizing straightforward Watson–Crick base pairing and their identification is fascinating. For me, switching from chemistry to biology is both exciting and enlightening. This study opens the way and helps me to grow and make my career in the field of chemical biology.

What do you hope to do next?

Of course, this is a tiny piece of work, and a lot of challenges have to be addressed in the field of DNA-based nano carrier from basic molecular biology to in vivo followed by advanced clinical level study. We are a multidisciplinary group dedicated to developing high-level DNA and peptide-DNA hybrid nanodevices for biological and biomedical applications.

Where do you seek scientific inspiration from?

As a scientist, I drew inspiration from a variety of sources. Reading research papers that discuss various problem-solving scientific tools inspires ideas. My Ph.D. adviser Dr. K B Joshi and my postdoc advisor Dr. Dhiraj Bhatia are constantly keen to explore new research topics and solve challenges with a high level of excitement. The many success stories that we encounter encourage me as well.

How do you intend to help Indian science improve?

India is gradually evolving as a leader in scientific research and dialogue. As a growing researcher, I always participate in scientific gatherings (workshops, conferences, etc) for exchange of dialogue and hence sharing and building knowledge among the scientific community. I believe in the power of collaboration with expert scientists in their respective fields in creating excellent scientific synthesis. I am always keen to support and discuss the research problem within my domain or expertise.

Reference

Ramesh Singh, Pankaj Yadav, Hema Naveena A, and Dhiraj Bhatia, Cationic lipid modification of DNA tetrahedral nanocages enhances their cellular uptake,
Nanoscale, 2023, Advance Article. https://doi.org/10.1039/D2NR05749B

Copy Editor

Nivedita Kamath

Postgraduate in Biotechnology

Nivedita is a Postgraduate in Biotechnology, with one year Project Assistantship experience at inStem, DBT. She is currently a UPSC aspirant planning to appear for 2021 CSE. Although switching from science career to focus on governance policy and administration, her love for science remains ever-etched in all that she does. On her journey from a researcher toward public administrator, she believes in the critical role of science communication and journalism in bridging the gap between lab benches and public fields. Being part of BioPatrika is her being one stone laid for that very bridge.

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