Can CrisprBits Make Critical Disease Diagnosis Faster And Cheaper?

It’s elementary! Feluda, Satyajit Ray’s iconic Indian detective, will follow his godfather Sherlock Holmes. 

What’s intriguing is their association, breaching nearly 100 years between them, in cracking the mysteries of nature that roil mankind.

In the backdrop of the Covid pandemic, the Feluda test, abbreviated from FnCas9 Editor Linked Uniform Detection Assay, became one of the world’s first CRISPR-based diagnostic tests. It was being developed and carried out by two researchers at CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB). 

CRISPR – an acronym for Clustered Regularly Interspaced Short Palindromic Repeat – helped the researchers find a rapid, highly accurate tool that could detect the SARS-CoV-2 virus without the need for complex lab equipment. 

The Covid pandemic of 2020-21 showed the world the fragility of our conventional diagnostic systems at times of heavy rush. CRISPR-based diagnosis quietly stepped out of research labs and moved straight to the frontline of public health. 

The Feluda test came after Sherlock – anagrammed from Specific High-Sensitivity Enzymatic Reporter unLOCKing – and DNA Endonuclease Targeted CRISPR Trans Reporter, or DETECTR (pronounced detector), which were being carried out in the US. 

These developments followed the path of Emmanuelle Charpentier and Jennifer Doudna, who won the 2020 Nobel Prize in chemistry for their decade-long work on CRISPR-Cas9.

Away from all the buzz, Bengaluru-based CrisprBits started taking baby steps around the same time towards building platforms that could detect diseases like sickle cell and typhoid, using the CRISPR technique. 

“It was already in the air that CRISPR-based techniques could change the shape of diagnostics. Be it Feluda or Sherlock, the adaptations of CRISPR for diagnostics, only established that fact further. There were also works going on in the industrial application of the technique globally. And we followed the path,” Dr Vijay Chandru, cofounder of CrisprBits, told Inc42.

“The Covid-19 pandemic has been a pivotal point in how India views technology, innovations, and biosecurity. For us, too, it was pivotal. After decades of work in molecular biology, and some research on CRISPR over the years, we decided to start building new diagnostic toolkits that could one day give the same or higher accuracy than the RT-PCR tests, at the bedside.”

Five years on, the startup is set to start commercialisation of its diagnostic platform, PathCrisp. 

CrisprBits recently raised $3 Mn (INR 26.8 Cr) in a pre-Series A round from Spectrum Impact, promoter family of HBL Engineering and C-CAMP (Centre for Cellular and Molecular Platforms), to commercialise its PathCrisp molecular diagnostics platform.

The Building Blocks Of Life

Five deeptech and entrepreneurial brains – Dr Chandru, Sunil Arora, Dr Rajeev Kohli, Bharat Jobanputra, and Aditya Sarda, all BITS Pilani graduates from the 1970s – converged on CRISPR. 

Dr Chandru, who had earlier founded biotech startup Strand Life Sciences, comes from a biotech background, but the other four have diverse backgrounds. While Dr Kohli is a professor at Columbia Business School, Jobanputra has served as vice-president for projects at Canadian deeptech company Forderanlagen Magdeburg GmbH. Arora and Sarda, on the other hand, come from manufacturing industries.

While the team had started doing some research on the CRISPR technique in early 2020, CrisprBits came up in October. After more than two years of discussions, refining the platform ideas, aligning the core team members on the product-building goal, and conducting initial R&D, full-fledged operations finally began in 2023.

It soon began building the toolbox, or kit, as they call it, containing enzymes, capabilities, assays, and guides for various human mutations, pathogens, and pathogen modifications, and other elements — essentially, a collection of CRISPR-based systems that would later provide flexibility in leveraging the technology in different ways.

While doing diagnostics, CrisprBits saw opportunities to use the technology in editing genes of organisms and cell lines to optimise various bio-industrial processes, for producing biochemical products such as biofuels. 

This also led the founders to think of curing genetic disorders using the technology.

CrisprBits today works on three platforms – PathCrisp for diagnostic needs, EdiCrisp for gene editing in industrial processes, and CurieCrisp that is touted as a future solution for curing genetic disorders.

While CurieCrisp is more in the initial days of its R&D, the first two platforms are ready for commercialisation.

A few tests offered by PathCrisp are under trial at various hospitals across India, while some are in the labs. “There will be a series of products that will come up. In fact, we have a strong pipeline and the fundraise will allow us to commercialise and manufacture to take these kits to the market,” Dr Chandru said.

On the other hand, it has started generating a small amount of revenue leveraging its EditCrisp platform, where it provides gene editing services to academia, pharmaceutical companies, and helping them produce proteins faster for different industrial applications and build IPs.

Decoding CRISPR And CrisprBits Tech

What is this buzz over CRISPR all about? Put precisely, it is an immune system, which was originally discovered in microbes. “It’s used by microbes to help protect themselves from invading viruses. To stop the invaders, the microbes use CRISPR to recognise and eliminate specific trespassers,” Stanford biologist Stanley Qi had said. 

Explaining this phenomenon, which takes place in nature, CrisprBits chief scientific officer Dr Vaijayanti Gupta, said that when a bacterium survives the attack of a virus, it takes pieces of the viral DNA or nucleic acid and stores it in its own genome. Later on, when a phage virus attacks it again, it recounts the DNA code sequence and senses a threat. This way, the virus attack is prevented. “It’s like adaptive immunity.” 

The two Nobel laureates essentially characterised this entire process. “They took out this system from the bacteria and showed that its specificity exists not only for phages and within the bacterial system, but if we isolate that enzyme and this entire machinery, we can target pretty much anything – any piece of DNA, any mammalian cell, another bacteria, a fungi, a plant,” she said.

CrisprBits has turned the act of finding a specific piece of genetic material or pathogen into a clear, visible readout, making diagnostics faster, simpler, and highly accurate. The test kits, containing samples of protein, paper strips found in any rapid PCR testing kits, CrisprBits’ proprietary reagent solutions, and a portable qPCR machine, are more usable, anywhere, anytime, claimed the founders. 

“Diagnostic labs send samples in ice or dry ice in minus-20 degrees Celsius. We have been carrying these kits with us in our suitcases at room temperature. We have even shipped them to Kenya and other countries just like that,” Dr Gupta said, adding that the tests using its PathCrisp platform can be conducted at diagnostic centres and even deployed at any point of need.

CrisprBits also wants to make it easily accessible even to farmers for quick disease detection in crops and animals. 

It claims that the process is faster and less expensive than other genome tests or regular blood culture procedures. Its diagnostic process, for instance, would cost around INR 500-800, while normal Sanger sequencing used for various types of genetic testing can cost INR 1,500-2,000 in India.

Regular diagnostic reports take 12-72 hours, depending on the testing method. The faster tests are often accompanied by a high rate of inaccuracy. “We want to help patients get a typhoid report in half a day with 100% accuracy. That’s our target,” Dr Gupta said. 

The startup is using the same technique in gene editing as well. Biofuel or biogas production relies on a complex mix of bacteria, each playing a specific role in breaking down the waste. To boost efficiency, researchers are now engineering these strains to work faster, produce fewer toxins and deliver better output.

EdiCrisp is enabling these processes. “With the latest fund, we also want to increase focus on engineering strains for better biofuel, particularly aviation fuel,” he said.

Racing On A Simmering Biotech Turf

The startup’s idea from here on is to keep expanding its portfolio across platforms. “In the next 12 months, you will definitely see our antimicrobial resistance and the ESKAPE pathogen detection tests, as well as the sickle cell and haemoglobinopathy detection test in the market, not just in India, even outside, in low- and middle-income countries and regions,” the chief scientific officer said.

Research shows that India makes up 14.5% of sickle cell newborns globally, estimated at over 42,000 a year, followed by sub-Saharan Africa.

CrisprBits’ food testing is also entering a beta-testing phase in collaboration with the Central Food Technological Research Institute (CFTRI), which is also expected to hit the market next year.

The startup is executing some cancer research in parallel. “On the gene editing side, we are partnering with a few established cancer research companies to produce more efficient, next-generation CAR-T cells for cancer treatment,” she said.

CrisprBits has filed for three major patents so far, including a test for the SARS-CoV-2 virus filed in India, a test for acute respiratory illness and sickle cell, both of them are in the US and India. None of the patents are granted yet. 

But now there’s a sudden rise in companies and labs working with the CRISPR technique. Besides India’s Feluda, which has started commercialising in many areas, biotech major Biocon’s Syngene is working on this technology, which is purely working in a services model. 

The government has also started pushing for CRISPR with the launch of an indigenous CRISPR platform, BIRSA 101, developed at CSIR–IGIB. Companies like CRISPR Therapeutics, MicroCrispr, Krispr, Mammoth Biosciences’ Sherlock, as well as large pharma companies, including Merck, Thermo Fisher, and Danaher, are working in this area to capture a burgeoning CRISPR and Cas Genes market that is expected to touch $27.3 Bn by 2030.

CrisprBits is confident that India is well-positioned to capture a global market where there is a huge whitespace. “There may be a few other smaller companies working on therapeutics, but no team is trying to build master platforms like us across diagnostics, therapeutics, and strain engineering,” Dr Chandru said. 

In the international market, Mammoth and Sherlock had been spin-offs from Berkeley and Dana-Farber, but diagnostics is not a popular business to scale in the US owing to a stronger focus on therapeutics and the insurance models. Mammoth shut down its diagnostics business, and Sherlock is also quieter, although they did take the SARS-CoV-2 test through the FDA and launched a Zika virus test kit.

Genes don’t determine destiny, but decoding genes helps cracking the mystery to ensure a healthier life. That’s where CrisprBits bets big as biotech grows to be a $3.9 Tn industry by 2030.    

[Edited By Kumar Chatterjee]