Clustered regularly interspaced short palindromic repeats (Crispr) and its associated protein (Cas9) have been generating quite a buzz of late, even resulting in speculation about a new technology race between the US and China. Political and strategic implications apart, scientists all over the world are now able to carry out gene editing at costs much lower than ever before, and much more accurately. The enhanced tinkering with deoxyribonucleic acid (DNA)—the building blocks of life—can be used to achieve end goals as diverse as enhancing crop quality and disease resistance, treating genetic diseases, and even addressing the associated risk of antibiotic resistance through a Crispr pill that substitutes antibiotics.
But the media attention hogged by this technology should not blind us to new advances in ribonucleic acid (RNA) research. This polymeric molecule—essential for regulation and expression of genes—has already been the subject of research, in areas such as RNA interference (RNAi) and antisense technology. While RNAi is a gene silencing technology that inhibits protein synthesis in target cells using double-stranded RNA, antisense technology achieves the same result through single-stranded RNA.
RNAi has huge significance within the Indian context, considering the deep-seated resistance over the years to Bt cotton and other genetically modified seeds. Recently, genetically modified mustard received regulatory approval from the genetic engineering appraisal committee, only to get stalled later on account of a petition filed before the Supreme Court. While it is imperative that India develops a more scientifically informed approach to regulating genetically modified crops, RNA-reliant solutions could be a viable alternative.
In addition, RNAi technologies are now known to formulate drugs capable of reducing cholesterol levels by half. This technology also finds immense importance in treating acute viral infections like acquired immunodeficiency syndrome (AIDS), perhaps because of the well-studied life cycle and pattern of gene expression of the human immunodeficiency virus (HIV).
Antisense technology has shown promising results in producing a variety of tomato with increased shelf-life commonly known as Flavr Savr. The future could potentially be witness to the use of antisense technology to target cancer.
While there are quite a few successful companies working with RNAi and antisense technologies abroad, the major constraint hampering progress in these fields in India is the poor translation of this nucleic-acid based therapy to clinical studies. India faces two major challenges hindering progress in RNAi and antisense technologies.
First is the lack of efficient and targeted delivery vehicles for these potential RNA molecules. While, the Institute of Chemical Technology, Mumbai, Indian Institute of Science Education and Research, Thiruvananthapuram, and Indian Institute of Science, Bengaluru, have developed drug delivery vehicles capable of delivering proteins, much less has been done to develop vehicles capable of carrying silencing reagents such as small interfering RNA (siRNA). Though this is one of the objectives of a stand-alone programme on nano-biotechnology under department of biotechnology, research gaps continue to exist.
Second, the relatively minimal development of silencing reagents that ensure significant, specific, consistent and lasting knockdown of the target gene. The drug controller general of India (DCGI) has granted its nod to the first-ever clinical trial of siRNA therapy in India developed by Biocon in collaboration with Quark Pharmaceuticals, US, in 2016. The number of such trials is negligible when compared to the total number of clinical trials in our country.
India, in order to deal with the first constraint, needs to develop domestic facilities focusing on nanotechnology-based targeted RNA-delivery product development. Nanotechnology being a multidisciplinary field must evoke cooperation and partnership among government ministries (both at the Central and state level), research organizations, and private sector donors. At all levels of government, there must be active collaboration with research institutions in the US, Russia, Japan, and other early movers in this space, in terms of the training and development of human resources. Academic institutions and governmental agencies must organize nationwide seminars and symposiums to highlight the importance of nanotechnology in the fourth industrial revolution.
In order to address the second challenge, India must enhance its competence around bioinformatics. Start-ups in the bioinformatics field must work on developing design algorithms for the development of safer, less toxic and more stable silencing reagents. While India has seen some progress in this area, sustainable improvements in bioinformatics research would require an increased number of trained scientists becoming experts in the discipline.
With the advances in nanotechnology and bioinformatics in place, India can be an attractive destination for a number of multinational pharma companies to either outsource some part of their research to India or buy the siRNA products or nano-carriers for RNA delivery from India. This can give a significant push to India’s gross domestic product (GDP) as well as help Indian companies do more innovative work in this space through knowledge-sharing and collaborations.